The Sierra Mixe or Mixes District is a district in the east of the Sierra Norte Region of the Mexican state of Oaxaca. It comprises 17 municipalities and covers 4,930 square kilometers (1,900 square miles) at an average elevation of 1,200 meters (3,900 feet) above sea level. As of 2020 the district had a total population of 112,447. The main food crops are maize and beans, while permanent crops include coffee, lemon and oranges.

Most of the inhabitants are of indigenous Mixe ethnicity, and the Mixe languages are spoken throughout the region. The western part of the region is high Sierra, with climate ranging to temperate to cold with strong winds and seasons of daily and constant rains and storms, this changes to the Mixe media territories; of lower mountain ranges but still a very abrupt and rough terrain, with daily rain, ranging from tropical to mist forests to pine-encine^{[check spelling]}, but the more eastern parts are the tropical lowlands of the Isthmus of Tehuantepec.

The district includes the following municipalities: