Although previous findings identified an association between C-reactive protein (CRP) levels, and impaired cognitive functions in patients with schizophrenia (SZ), little is currently known about the relationship between inflammation, cognition, and sex in SZ. The current study aimed to explore the association between peripheral inflammation and cognitive impairment in SZ as a function of sex. The sample included 132 clinically stable patients with SZ, of whom 82 were males (62.1%) and 50 females (37.9%). Sociodemographic data were collected, an accurate assessment was performed using the Positive and Negative Syndrome (PANSS), Clinical Assessment Interview for Negative Symptoms (CAINS), and Calgary Depression (CDS) scales, and the MATRICS Consensus Cognitive Battery (MCCB), and CRP levels were tested. A Pearson correlation and multiple regression analyses, including potential confounding factors, were performed. We found an inverse association between CRP levels and performance on visual learning (r = - 0.386, p = 0.006) domain in female patients only, whereas no correlations were found in males. The regression model for women retained age (β = - 0.319, p = 0.017), the CAINS-MAP score (β = - 0.247, p = 0.070), and the CRP (β = - 0.321, p = 0.013) as predictors of visual learning. Our results suggest the possible existence of sex-specific modulation of the association between systemic inflammation and the cognitive features of the illness.