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Objective To investigate the relationship between serum selenoprotein S (SelS) and obesity in patients with type 2 diabetes mellitus (T2DM). Methods Two hundred and nine T2DM patients who were managed by the National Metabolic Management Center (MMC) of the First Affiliated Hospital of Dalian Medical University from November 2017 to November 2019 and 55 healthy people as controls in the health examination center of our hospital were enrolled in the retrospective cross-sectional study. The general condition, biochemical indexes and obesity evaluation parameters were recorded. According to the serum SelS quartile, T2DM patients were divided into Q1 group: ≤95.10 ng/dl (53 cases), Q2 group: 95.12 to 111.62 ng/dl (52 cases), Q3 group: 112.46 to 130.97 ng/dl (52 cases), Q4 group: ≥131.33 ng/dl (52 cases). Analysis of variances, rank sum test and Chi-square test were used for comparison between groups. Multiple stepwise regression was used to analyze the influencing factors of obesity evaluation index. Results There was statistically significant difference in visceral fat index (VAI) among T2DM abdominal obesity group, non-abdominal obesity group and healthy control group (H=36.679, P<0.01), but there was no statistically significant difference in serum SelS. There was statistically significant difference in serum amyloid A (SAA) level among the SelS quartile groups (H=3.560, P<0.01), but there was no statistically significant difference in visceral fat area (VFA), subcutaneous fat area (SFA), visceral fat area to subcutaneous fat area ratio (VSR) and VAI. Serum SelS was positively correlated with VFA, VSR, VAI and SAA (r=0.158 to 0.448, all P<0.05). Serum SelS was an independent risk factor for VFA (β= 0.172, P=0.003), VSR (β=0.001, P=0.01) and VAI (β=0.009, P=0.038). Conclusion Serum SelS level in T2DM patients is positively correlated with VFA, VSR and VAI, which is an independent risk factor for abdominal obesity. [ABSTRACT FROM AUTHOR]