Panthera onca mesembrina, also known as the Patagonian panther, is an extinct subspecies of jaguar (Panthera onca) that was endemic to southern Patagonia during the late Pleistocene epoch. It is known from several fragmentary specimens, the first of which found was in 1899 at "Cueva del Milodon" in Chile. These fossils were referred to a new genus and species "Iemish listai" by naturalist Santiago Roth, who thought they might be the bones of the mythological iemisch of Tehuelche folklore. A later expedition recovered more bones, including the skull of a large male that was described in detail by Angel Cabrera in 1934. Cabrera created a new name for the giant felid remains, Panthera onca mesembrina, after realizing that its fossils were near-identical to modern jaguars'. P. onca mesembrina's validity is disputed, with some paleontologists suggesting that it is a synonym of Panthera atrox.

The bones of P. onca mesembrina are nearly double the size of the largest living jaguars (P. onca onca), and estimates place it at over 231 kilograms (509 lb) in weight. This would make it the largest jaguar and one of the heaviest known felids. Fragments of skin have been collected from "Cueva del Milodon", showing that it was dark red with lighter, yellowish stripes on its forelimbs. Cave paintings made by indigenous peoples possibly depicting the animal have been found in the El Ceibo, which features a red coat with stripes and spots. P. onca mesembrina was carnivorous and hunted a variety of large mammals, including the ground sloth Mylodon, horse Hippidion, and camelid Lama.

Near his farm in the mountains of Última Esperanza Province, Chile, German explorer Hermann Eberhard came across a cave bearing fossils of the ground sloth Mylodon, leading it to be dubbed "Cueva del Milodón". These fossils date to the late Pleistocene, making them as recent as 12,000 BP, dating them to the Lujanian SALMA (South American Land Mammal Ages; a series of fauna-based geological ages). In March of 1899, Swedish adventurers Erland and Otto Nordenskjöld found a radius and ulna that they assigned to a jaguar. Later that year, German naturalist Rodolfo Hauthal [de] and his crews found several isolated postcranial elements coming from a giant felid, which he donated to the Museo de La Plata (MLP).

At the MLP, the museum's director Santiago Roth described the fossils in 1899 as being from a novel genus and species of feline, which he designated "Iemish listai". This name references iemisch, a mythological monster of native Patagonian folklore. Roth noted that the size of the fossils fit descriptions of the myth made by Tehuelche locals and by Argentine naturalist Florentino Ameghino in the 1880s. This led Roth to believe it could still be living, which was further supported by a Tehuelche story about an extant individual that lived near Lake Buenos Aires. However, this name is now considered a nomen nudum (invalid name) as Roth based it on the legends and fossils, violating Article 72.5 of the ICZN, which stipulates that species can only be based on physical specimens or depictions. The next year, English paleontologist Arthur Smith Woodward assigned the material to Felis, noting the bones' similarities to those of extant jaguars. Later that year, Hauthal collected additional felid elements from the cave including a partial skull, two mandibles (lower jaws), other postcranial remains, and isolated portions of skin. In 1904, Roth described the remains and, following Woodward's hypothesis, abandoned the genus name "Iemish" and instead made "I. listai" a species of Felis, but argued that it was distinct from Felis onca due to its size.

In 1934, an analysis by Argentine paleontologist Angel Cabrera concluded that some of the bones described were from Neomylodon, a synonym of Mylodon. Furthermore, he stated that because Iemish was a title used for the mythical beast recorded by Ameghino and for the Neomylodon material, the name should be considered invalid. He went on to note that the bones were near identical to those of modern jaguars, though size was greater than that of any known jaguar. Due to "Iemish listai" being unusable, he proposed a new name, Panthera onca mesembrina, with the incomplete skull (MLP 10-90) selected as the holotype (name-bearing) specimen. The subspecies name mesembrina derives from the Greek word mesembrinos, which translates to "southern". This is due to the origin of the fossils, which come from Patagonia in southern Argentina. The holotype was subsequently lost, but both Cabrera and Roth published illustrations of it. Cabrera stated that the jaguar may have been seen or hunted by native peoples, stating that a pathology on the skull matched those characteristic of arrow wounds. More fossils were later found at the cave, including feces. Caves across Patagonia produced additional fossils, including those of juveniles and elderly individuals. In a cave near Sofia Lake, many isolated specimens from juveniles were unearthed.

A 2016 study of a mitochondrial DNA sequence obtained from bones attributed to P. onca mesembrina found that they represented those of a true jaguar, but belonged to a mitochondrial lineage highly divergent from those found in living jaguars. This supported its validity and independence from other P. onca subspecies. However, in 2017 morphological research of the holotype and other remains by Chimento et al instead referred it to the lion relative Panthera atrox. This conclusion has seen acceptance by some authors. In his 2020 thesis, researcher Nicholas Freymueller argued that this could be a case of Bergmann's rule, as traits correlated with larger body size were used to justify the synonymy in Chimento et al's study. In 2024, it was suggested that the validity of subspecific assignments on both P. o. mesembrina and the North American P. o. augusta remains unresolved, since both fossil and living jaguars show a considerable variation in morphometry.

Panthera onca mesembrina is the largest subspecies of P. onca, with a 2017 estimate placing its body mass at 231 kilograms (509 lb) based on the type material. This makes it not only the heaviest known jaguar by as much as 90 kilograms (200 lb), but one of the largest known felids. The trend of large body size among Pleistocene felids was likely due to a multitude of factors such as: prey size, environmental conditions of the epoch, and, for P. onca mesembrina specifically, Bergmann's Rule. A similar trend of gigantism is observed in the North American subspecies P. o. augusta, which was around 15-20% larger than modern jaguars at around 190 kilograms (420 lb). P. onca mesembrina shared the robust, stocky build of P. onca onca but to an even greater degree.

P. o. mesembrina and P. o. augusta share many similarities that are lacking in living jaguars, such as on the skull, with the presence of exposed foramina (small holes) near the nasal (nose bone) and an expanded nasal aperture (nose opening). While the skulls of extant P. onca onca individuals are short, heavy, and wider at the end of the snout, P. onca mesembrina's skull had a longer snout which tapered slightly at the premaxilla. The teeth of P. onca mesembrina were remarkably large compared to those of other Panthera species, a trait shared by living jaguars. However, few teeth are known from this subspecies. In the first molar, the paraconid (mesial cusp) is much shorter than the protoconid (distal cusp), a feature present in P. atrox and P. onca mesembrina but absent in most other pantherines.