The Middle Eocene Climatic Optimum (MECO) is a global warming event that occurred at about 40 Ma. In comparison to the most known global warming events of the Paleogene, the MECO has some peculiar features that make its interpretation controversial. The main peculiarities of the MECO are a duration of ~500 kyr and a carbon isotope signature that varies from site to site. Here we present new carbon and oxygen stable isotopes records (δ13C and δ18O) from three foraminiferal genera dwelling at different depths throughout the water column and the sea bottom during the middle Eocene, from eastern Turkey. We document that the MECO is related to major oceanographic and climatic changes in the Neo-Tethys and also in other oceanic basins. The carbon isotope signature of the MECO is difficult to interpret because it is highly variable from site to site. We hypothesize that such δ13C signature indicates highly unstable oceanographic and carbon cycle conditions, which may have been forced by the coincidence between a 400 kyr and a 2.4 Myr orbital eccentricity minimum. Such forcing has been also suggested for the Cretaceous Oceanic Anoxic Events, which resemble the MECO event more than the Cenozoic hyperthermals.