Adiponectin is an important marker of anthropometric profiles of adipose tissue. However, association of adiponectin and adiposity in HIV mono- and co-infected and hepatitis (HCV) injection drug users (IDUs) has not been elucidated. Therefore, the relationship of total adiponectin levels with anthropometric indices of adiposity was examined in HIV mono-infected (anti-retroviral treatment, ART-naive, n=16 and -experienced, n=34); HCV mono-infected, n=36; HIV and HCV co-infected (ART-naive, n=5 and -experienced, n=13); uninfected, n=19 IDUs; and healthy controls, n=16 from coastal Kenya. Anthropometric indices of adiposity were recorded and total circulating adiponectin levels were measured in serum samples using enzyme-linked immunosorbent assay. Adiponectin levels differed significantly amongst the study groups ( P<0.0001). Post-hoc analyses revealed decreased levels in HIV mono-infected ART-naive IDUs in comparison to uninfected IDUs ( P<0.05) and healthy controls ( P<0.05). However, adiponectin levels were elevated in HCV mono-infected IDUs relative to HIV mono-infected ART-naive ( P<0.001) and -experienced ( P<0.001) as well as HIV and HCV co-infected ART-naive ( P<0.05) IDUs. Furthermore, adiponectin correlated with weight ( ρ=0.687; P=0.003) and BMI ( ρ=0.598; P=0.014) in HIV mono-infected ART-naive IDUs; waist circumference ( ρ=−0.626; P<0.0001), hip ( ρ=−0.561; P=0.001) circumference, and bust-to-waist ratio ( ρ=0.561; P=0.001) in HIV mono-infected ART-experienced IDUs; waist girth ( ρ=0.375; P=0.024) in HCV mono-infected IDUs; and waist-to-hip ratio ( ρ=−0.872; P=0.048) in HIV and HCV co-infected ART-naive IDUs. Altogether, these results suggest suppression of adiponectin production in treatment-naive HIV mono-infected IDUs and that circulating adiponectin is a useful surrogate marker of altered adiposity in treatment-naive and -experienced HIV and HCV mono- and co-infected IDUs.