An activation of pro–inflammatory cytokines in the central nervous system is associated with cognitive disturbances. This process is mediated by prostaglandins and cyclo–oxygenase–2 (COX–2). COX–2 inhibitors have been suggested to show beneficial effects in disorders associated with cognitive disturbance, although clinical effects on cognition have not been shown until today. Data from a schizophrenia study were reevaluated under the aspect whether an effect on the positive and negative syndrome scale (PANSS) factor cognition can be observed during therapy with the COX–2 inhibitor celecoxib add on to risperidone in comparison to riperidone alone. Beside the effect on the PANSS total score, the effect on the cognition factor was the most pronounced using the analysis of covariance compared to all other factors of the PANSS (p <0.06). Although suggestions of basic research led to an expected therapeutic effect of COX–2 inhibitors on cognition, this effect could not yet be shown clinically. In schizophrenia, the effect on cognition contributes to the therapeutic effect of COX–2 inhibitors.