There is evidence suggesting that some patients with schizophrenia have increased circulating pro-inflammatory markers present in their serum. We hypothesize that serum soluble interleukin-2 receptor (sIL-2r) levels may serve as a biomarker for a subset of patients with schizophrenia. Serum sIL-2r levels were serially sampled from 59 medically stabilized subjects with schizophrenia and 57 control subjects. Serum sIL-2r levels were consistently elevated for subjects with schizophrenia when compared to controls. This finding was driven by a subgroup of patients (16/59) who had serum sIL-2r levels two standard deviations beyond the mean of the control sample. Elevated serum sIL-2r levels were associated with increased Positive and Negative Syndrome Scale total scores, negative symptom and general psychopathology subscale scores. These results suggest that a subset of patients with schizophrenia have an elevation in a marker of immune activation that is stable over time and is associated with increased levels of psychopathology.