Objectives The objective of this study was to determine whether prolactin levels are associated with a pro-inflammatory body mass distribution in women with systemic lupus erythematosus (SLE). Methods This cross-sectional study was conducted in consecutive female SLE patients seen in our rheumatology department from January 2012 to July 2015. Prolactin was measured in ng/ml. Body mass distribution was measured by dual energy x-ray absorptiometry and it was divided into subtotal (whole body excluding the head), subtotal bone mineral content, lean mass index (appendicular lean mass/height2), subtotal trunk and leg fat percentages and trunk-to-leg fat ratio. The association between prolactin levels and body mass distribution components was evaluated by univariable and multivariable linear regression models adjusting for possible confounders. Results One hundred and eighty-five patients were evaluated; their mean (SD) age at diagnosis was 34.8 (13.8) years; nearly all patients were Mestizo. Patients included in this study were comparable to the rest of the cohort in terms of age, disease duration, SLEDAI, SDI and body mass index. Disease duration was 7.3 (6.6) years. The SLEDAI was 5.2 (4.3) and the SDI 0.9 (1.3). Prolactin levels were 18.9 (16.7) ng/ml. In univariable analyses, prolactin was negatively associated with bone mineral density, bone mineral content, leg fat percentage and lean mass index, and positively associated with trunk-to-leg fat ratio. In the multivariable analyses, prolactin was negatively associated with bone mineral content and positively associated with trunk-to-leg fat ratio. Conclusions Higher prolactin levels are associated with a pro-inflammatory body mass distribution in SLE patients.