The changes in macrofauna and microfauna, before, during and after the latest Cenomanian global Oceanic Anoxic Event (OAE2), from the Eastern Desert of Egypt are documented, along with an inferred paleoenvironment. The age of the studied OAE2 interval is constrained by the last occurrence of the marker calcareous nannofossils species Axopodorhabdus albianus along with the previously identified positive δ13C excursion from the coeval ammonite Vascoceras cauvini Zone (= Neocardioceras juddii Zone), enabling correlation with the peak ‘b’ of the OAE2. Based on the studied microfaunal assemblages, a warm shallow restricted lagoonal environment with mesotrophic conditions and strong seasonality is inferred. The presence of a rare ammonite (and ostracods) attest to the intermittent introduction of marine waters within this inner ramp setting. In terms of sequence stratigraphy, two 3rd order depositional sequences are recorded. The top surface of the first depositional sequence, at the sequence boundary, SB Ce 5 (the start of the OAE2), is marked by an abrupt faunal change with reduced abundances of the macrofaunal elements. This is in tune with other Egyptian records of relatively smaller loss (10 %) at the Cenomanian-Turonian boundary, as compared to much higher numbers (53–79% of species), globally. This faunal (biotic bottleneck) and lithological change (from siliciclastic-dominated deposits to a largely carbonate-dominated one) at the SB Ce 5 is attributed as a response to the latest Cenomanian drowning (the highest sea-level during the Phanerozoic), that also resulted in the formation of carbonate platform.