ObjectiveWe addressed elevated C-reactive protein level (eCRP) specificity comparing, for the first time, eCRP (i.e., serum CRP > 3 and ≤10 mg/L) in patients with major depressive disorder (MDD), bipolar disorder (BD), or obsessive–compulsive disorder (OCD). We also assessed to what extent multiple variables that can potentially increase inflammation may have influenced eCRP in our sample. MethodsWe performed a retrospective, observational, cross-sectional study using information documented in the electronic medical records (EMRs) of patients hospitalized for a 4-week psychiatric rehabilitation program. We collected all information according to the standardized procedures of the hospital's clinical practice and applied a logistic regression model (α = 0.05). ResultsWe included 388 inpatients, that is, 156 (40.2%) with MDD, 135 (34.8%) with BD, and 97 (25.0%) with OCD, and found considerable eCRP rates among them (36.5%, 47.4%, and 29.9% in MDD, BD, and OCD, respectively) but without significant differences across groups. In the whole sample, eCRP variations were only partially attributable (approximately for one-third) to potential confounders. All groups presented considerable rates of cardiovascular risk factors, and we classified most patients as having medium or high CRP-based cardiovascular risk. ConclusionThis first study comparing eCRP in MDD, BD, and OCD suggests that eCRP may be a transdiagnostic feature of different psychiatric disorders, and other mechanisms beyond the effects of multiple confounders may explain the presence of eCRP in a substantial portion of psychiatric patients. Therefore, we encourage the routine measurement of CRP in psychiatric clinical practice.