Emerging evidence indicates that obesity impairs granulosa cell (GC) function, but the underlying mechanisms remain unclear. Gene expression profiles in GC of non-polycystic ovary syndrome (PCOS) obese (NPO), PCOS obese (PO), PCOS normal weight (PN) and non-PCOS normal weight (NPN) patients were analysed by microarray analysis. Compared with the NPN group, there were 16, 545 and 416 differently expressed genes in the NPO, PO and PN groups respectively. CD36 was the only intersecting gene, with greater than two fold changes in expression between the NPO versus NPN and PO versus NPN comparisons, and was not present in the PN versus NPN comparison. In addition, levels of CD36 protein were higher in GC from obese than normal weight patients. Furthermore, CD36 overexpression in a GC line inhibited cell proliferation, as determined by the cell counting kit-8 (CCK8) test, promoted cell apoptosis, as determined by flow cytometry, and inhibited the secretion of oestradiol by depositing triglyceride in cells and increasing cellular lipid peroxide levels. These adverse effects were reduced by sulfo-N-succinimidyloleate, a specific inhibitor of CD36. Together, the findings of this study suggest that obesity with and without PCOS should be regarded as separate entities, and that CD36 overexpression in GC of obese patients is one of the mechanisms by which obesity impairs GC function.