It is unclear how rising obesity among people with HIV (PWH) impacts their risk of type 2 diabetes mellitus (diabetes). We examined associations between HIV, prevalent diabetes and adiposity among South African PWH and their peers without HIV (PWOH). HIV status was ascertained by antibody testing. Diabetes was defined as current use of oral hypoglycemics, insulin, and/or HbA1c ≥6.5%. Adiposity was measured by body mass index (BMI), waist circumference and waist-to-height ratio. Their associations were examined using sex-stratified multivariable fractional polynomial generalized linear models, reporting adjusted prevalence and prevalence ratios (adjPR). The mean age among 1,254 PWH and 4,381 PWOH was 41 years (95%CI 28, 56). The prevalence of diabetes among males was similar between PWH [11.3% (7.1, 15.5)] and PWOH [9.8% (8.5, 11.1); p=0.740]. By contrast, diabetes prevalence was higher among female PWOH [15.7% (14.4, 17.0)] than female PWH [10.5 (8.3, 12.8)%; adjPR: 0.67 (0.51, 0.82); p<0.001]. This difference was accentuated with obesity but reversed with leanness. At BMI ≥25 kg/m2, female PWH had lower diabetes prevalence [adjPR: 0.58 (0.41, 0.76); p<0.001] than female PHIV. In contrast, at BMI <18 kg/m2, female PWH had higher prevalence [adjPR: 1.72 (-1.53, 4.96); p=0.756] than female PWOH. We found sex-specific differences in the relationship between adiposity and diabetes prevalence by HIV serostatus in South Africa. Notably, females living with obesity and HIV had lower prevalence of diabetes than females living with obesity and without HIV, which may have particular implications for diabetes prevention programs in the region.