In this paper, we discuss human occupation during the Early and Middle Holocene in the Eastern Desert of Egypt, based mainly on the data provided by excavated deposits from the Sodmein Cave, which produced an important Holocene stratigraphic sequence. This sequence is dated by a large number of conventional and AMS 14C dates. It appears that the area was empty of human occupation during the Late Glacial Maximum (LGM) and the earliest Holocene. With improved climatic conditions, humans arrived in the area, as hunter-gatherers using no ceramics, from around 7.1 to 6.4 Ka cal BC. Humans were absent from the cave during the Holocene 8.2 Ka event (ca. 6.3 Ka cal BC). From 6.2 to 5.0 Ka cal BC, herders visited the site on a regular basis importing caprines. The bone evidence for domesticated small stock is very limited at Sodmein but is nevertheless extremely important, as it contains the oldest known specimens for Africa to date. After 5.0 Ka cal BC, the area was almost entirely deserted.