Potosí Department is a department in southwestern Bolivia. It comprises 118,218 km² with 709,013 inhabitants (2001 census). The capital is the city of Potosí. It is mostly a barren, mountainous region with one large plateau to the west, where the largest salt flat in the world, Salar de Uyuni, is located.

Potosí was the richest province in the Spanish empire, providing a great percentage of the silver that was shipped to Europe.

It is also the location of the San Cristóbal silver, zinc and lead mines, developed by the US-company Apex Silver Mines Limited of Colorado and in November 2008 sold to the Japanese Sumitomo Corporation.