Objective Prolactin (PRL) is involved in immune regulation and may contribute to an atherogenic phenotype. Previous results on the association of PRL with inflammatory biomarkers have been conflicting and limited by small patient studies. Therefore, we used data from a large population-based sample to assess the cross-sectional associations between serum PRL concentration and high-sensitivity C-reactive protein (hsCRP), fibrinogen, interleukin-6 (IL-6), and white blood cell (WBC) count. Design and Population From the population-based Study of Health in Pomerania (SHIP), a total of 3744 subjects were available for the present analyses. Methods and Measurements PRL and inflammatory biomarkers were measured. Linear and logistic regression models adjusted for age, sex, body-mass-index, total cholesterol and glucose were analysed. Results Multivariable linear regression models revealed a positive association of PRL with WBC. Multivariable logistic regression analyses showed a significant association of PRL with increased IL-6 in non-smokers [highest vs lowest quintile: odds ratio 1 ·69 (95% confidence interval 1 ·10-2 ·58), P = 0 ·02] and smokers [OR 2 ·06 (95%-CI 1 ·10-3 ·89), P = 0 ·02]. Similar results were found for WBC in non-smokers [highest vs lowest quintile: OR 2 ·09 (95%-CI 1 ·21-3 ·61), P = 0 ·01)] but not in smokers. Linear and logistic regression analyses revealed no significant associations of PRL with hsCRP or fibrinogen. Conclusions Serum PRL concentrations are associated with inflammatory biomarkers including IL-6 and WBC, but not hsCRP or fibrinogen. The suggested role of PRL in inflammation needs further investigation in future prospective studies.