Eicosapentaenoic acid (EPA; also icosapentaenoic acid) is an omega−3 fatty acid. In physiological literature, it is given the name 20:5(n−3). It also has the trivial name timnodonic acid. In chemical structure, EPA is a carboxylic acid with a 20-carbon chain and five cis double bonds; the first double bond is located at the third carbon from the omega end.

EPA is a polyunsaturated fatty acid (PUFA) that acts as a precursor for prostaglandin-3 (which inhibits platelet aggregation), thromboxane-3, and leukotriene-5 eicosanoids. EPA is both a precursor and the hydrolytic breakdown product of eicosapentaenoyl ethanolamide (EPEA: C₂₂H₃₅NO₂; 20:5,n−3). Although studies of fish oil supplements, which contain both docosahexaenoic acid (DHA) and EPA, have failed to support claims of preventing heart attacks or strokes, a recent multi-year study of Vascepa (ethyl eicosapentaenoate, the ethyl ester of the free fatty acid), a prescription drug containing only EPA, was shown to reduce heart attack, stroke, and cardiovascular death by 25% relative to a placebo in those with statin-resistant hypertriglyceridemia.

EPA is obtained in the human diet by eating oily fish, e.g., cod liver, herring, mackerel, salmon, menhaden and sardine, various types of edible algae, or by taking supplemental forms of fish oil or algae oil. It is also found in human breast milk.

Fish, like most vertebrates, can synthesize very little EPA from dietary alpha-linolenic acid (ALA). Because of this extremely low conversion rate, fish primarily obtain it from the algae they consume. It is available to humans from some non-animal sources (e.g., commercially, from Yarrowia lipolytica, and from microalgae such as Nannochloropsis oculata, Monodus subterraneus, Chlorella minutissima and Phaeodactylum tricornutum, which are being developed as a commercial source). EPA is not usually found in higher plants, but it has been reported in trace amounts in purslane. In 2013, it was reported that a genetically modified form of the plant camelina produced significant amounts of EPA.

The human body converts a portion of absorbed alpha-linolenic acid (ALA) to EPA. ALA is itself an essential fatty acid, and humans need an appropriate supply of it. The efficiency of the conversion of ALA to EPA, however, is much lower than the absorption of EPA from food containing it. Because EPA is also a precursor to docosahexaenoic acid (DHA), ensuring a sufficient level of EPA on a diet containing neither EPA nor DHA is harder both because of the extra metabolic work required to synthesize EPA and because of the use of EPA to metabolize into DHA. Medical conditions like diabetes or certain allergies may significantly limit the human body's capacity for metabolization of EPA from ALA.

Commercially available dietary supplements are most often derived from fish oil and are typically delivered in the triglyceride, ethyl ester, or phospholipid form of EPA. There is debate among supplement manufacturers about the relative advantages and disadvantages of the different forms. One form found naturally in algae, the polar lipid form, has been shown to have improved bioavailability over the ethyl ester or triglyceride form. Similarly, DHA or EPA in the lysophosphatidylcholine (LPC) form was found to be more efficient than triglyceride and phosphatidylcholines (PC) in a 2020 study.

Aerobic eukaryotes, specifically microalgae, mosses, fungi, and most animals (including humans), perform biosynthesis of EPA usually as a series of desaturation and elongation reactions, catalyzed by the sequential action of desaturase and elongase enzymes. This pathway, originally identified in Thraustochytrium, applies to these groups:

Marine bacteria and the microalgae Schizochytrium use an anerobic polyketide synthase (PKS) pathway to synthesize DHA. The PKS pathway includes six enzymes namely, 3-ketoacyl synthase (KS), 2 ketoacyl-ACP-reductase (KR), dehydrase (DH), enoyl reductase (ER), dehydratase/2-trans 3-cos isomerase (DH/2,3I), dehydratase/2-trans, and 2-cis isomerase (DH/2,2I). The biosynthesis of EPA varies in marine species, but most of the marine species' ability to convert C18 PUFA to LC-PUFA is dependent on the fatty acyl desaturase and elongase enzymes. The molecule basis of the enzymes will dictate where the double bond is formed on the resulting molecule.