Mental disorders have been associated with increased levels of inflammatory markers, which can affect disease trajectories. We aimed to assess levels of C-reactive protein (CRP) and white blood cells (WBC) across individuals with schizophrenia, bipolar disorder, and depression, and to investigate associations with subsequent psychiatric admission and mortality.

We identified all adults in the Central Denmark Region during 2000–2012 with a first diagnosis of schizophrenia, bipolar disorder, or depression and a baseline measurement of CRP and/or WBC count. We followed these individuals until outcome of interest (psychiatric admission or death), emigration or December 31, 2012, using Cox regression analysis to estimate hazard ratios (HRs).

Baseline median CRP differed significantly between mental disorders (P = 0.01) being highest in individuals with bipolar disorder (3.5 mg/L) (particularly during manic states, 3.9 mg/L), followed by schizophrenia (3.1 mg/L), and depression (2.8 mg/L), while baseline WBC count did not differ (median 7.1 × 109/L). Elevated CRP levels were associated with increased all-cause mortality by adjusted HRs of 1.56 (95% CI: 1.02–2.38) for levels 3–10 mg/L and 2.07 (95% CI: 1.30–3.29) for levels above 10 mg/L compared to individuals with levels below 3 mg/L. WBC counts were not associated with all-cause mortality. No association was observed between levels of the inflammatory markers and subsequent psychiatric admissions.

People with severe mental disorders had increased inflammatory markers at first diagnosis, and elevated CRP levels were associated with increased mortality. Thorough screening for physical diseases is of utmost importance among individuals who are diagnosed with severe mental disorder.