Somatic symptoms are commonly seen in patients with major depressive disorder (MDD) and might be associated with inflammatory activation. Cytosolic phospholipase A2 (cPLA2) and cyclo-oxygenase-2 (COX-2) are the key enzymes in the metabolism of polyunsaturated fatty acids (PUFAs), which in turn may play an important role in inflammation and somatic symptoms in depression. This study investigated the effects of BanI polymorphism of cPLA2 gene and COX-2 rs4648308 genotypes on somatic symptoms and inflammatory marker in patients with MDD.Eighty-two patients with MDD were assessed for their psychopathology including 2 psychiatric and somatic symptoms, BanI polymorphism of cPLA2 and COX-2 rs4648308 genotypes and CRP levels. The results revealed that MDD patients with the cPLA2 BanI GG genotypes had higher somatic symptoms and higher levels of C-reactive protein (CRP), while no differences were found among the COX-2 rs4648308 genotypes. Inflammatory process, such as arachidonic acid cascade pathway, might help explain the effect of cPLA2 BanI polymorphism on the somatic symptoms, and may be a potential target for future investigation on treatment for MDD with somatic symptoms. However, the interpretation of the findings in this study is limited since we analyzed the data from a subset data from a larger study.