Burn wounds have a significant impact on the mental health of patients. This study aimed to investigate the impact of perceived social support and dispositional optimism on depression of burn patients. A total of 246 burn patients accomplished the Multidimensional Scale of Perceived Social Support, the Revised Life Orientation Test, and Depression Scale. The results revealed that both perceived social support and optimism were significantly correlated with depression. Structural equation modeling indicated that optimism partially mediated the relationship between perceived social support and depression. Implications for prevention of depression in burn patients were discussed.