Objectives We investigated the association between serum levels of C-reactive protein (CRP), a marker of inflammation, and the severity of psychopathology and cognitive impairment in schizophrenia. Methods We measured the levels of CRP in N =413 individuals with schizophrenia. Symptom severity was evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functioning with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Results The individuals with CRP ≥5.0 mg/μl had significantly lower RBANS cognitive scores than those with CRP <5.0 mg/μl (F =8.07, p <.005). However the CRP groups did not differ in the severity of positive, negative, or general PANSS symptoms (all p >.2). Conclusions Elevated serum levels of C-reactive protein in schizophrenia are associated with the severity of cognitive impairment but not of psychiatric symptoms. The long term consequences of elevated levels of CRP require further investigation.