In Zapotec cultures of Oaxaca (southern Mexico), a muxe (also spelled "muxhe") [muxeʔ] is a physically male individual who dresses and behaves in a feminine manner; they may be seen as a third gender. Some marry women and have children while others choose men as sexual or romantic partners. According to anthropologist Lynn Stephen, muxe "may do certain kinds of women’s work such as embroidery or decorating home altars, but others do the male work of making jewelry. Many now have white-collar jobs and are involved in politics."

The word muxe is thought to derive from the 16th century Spanish word for "woman", mujer.^{[citation needed]}

In contrast to Mexico's majority mestizo culture (where machismo prevails), the isthmus of Oaxaca has a predominantly Zapotec population, and it is widely reported that there is less hostility toward muxe in the region than homosexual, effeminate males and trans women face elsewhere in the strongly Catholic country. One study estimates that 6 percent of males in an Isthmus Zapotec community in the early 1970s were muxe. Other Zapotec communities have similar "third gender" roles, such as the biza’ah of Teotitlán del Valle.