This study examined pre-surgical depressed mood as a predictor of post-surgical memory change in adults who underwent temporal lobe resections (TLRs; n = 211). Patients completed the Wechsler Memory Scale-III and Beck Depression Inventory-Second Edition (BDI-II) before and after TLR (left = 110, right = 101) and were divided into two groups (clinically elevated depressive symptoms or not depressed) based on BDI-II score. Left-TLR patients with poorer pre-surgical mood had greater verbal memory declines after surgery compared with nondepressed left- or right-TLR patients and right-TLR patients with poor mood. Further, pre-surgical BDI-II score demonstrated incremental validity in predicting post-surgical memory change in left-TLR patients beyond pre-surgical memory scores. Differences in seizure outcome and post-surgical mood change could not account for memory decline. Results suggest that elevated pre-surgical depressive symptomatology is a risk factor for post-surgical memory decline and indicate that mood should be considered when advising patients about cognitive risks associated with temporal lobectomy. Results are discussed in terms of poor pre-surgical mood as an indicator of reduced cognitive reserve.