The pathophysiology of human immunodeficiency virus (HIV)-associated bone loss is complex and to date largely unknown. In this study, we investigated serum expression of microRNAS (miRNAs) linked to bone metabolism in HIV-associated bone loss. This was a case-control study. Thirty male individuals with HIV infection (HIV+) and osteoporosis/osteopenia (HIV+/OP+) (cases) and 30 age-matched male HIV+ individuals with normal bone mass (HIV+/OP-) (controls) were included in the analysis. Thirty male individuals matched for age without HIV infection (HIV-), were also included as second controls. The selected panel of miRNAs was as follows: hsa-miRNA-21-5p; hsa-miRNA-23a-3p; hsa-miRNA-24-2-5p; hsa-miRNA-26a-5p; hsa-miRNA-29a-3p; hsa-miRNA-124-3p; hsa-miRNA-33a-5p; and hsa-miRNA-133a-3p. Within the cohort of HIV+ individuals, relative serum expression of miRNA-21-5p and miRNA-23a-3p was significantly lower ( < 0.001) while the expression of miRNA-24-2-5p was significantly higher ( = 0.030) in HIV+/OP+ compared to HIV+/OP-. Expression of miRNA-21-5p demonstrated a sensitivity of 84.6% and a specificity of 66.7 in distinguishing HIV+/OP+ individuals. Expression of circulating miRNAs related to bone metabolism; miRNA-23a-3p, miRNA-24-2-5p, and miRNA-21-5p is significantly altered in HIV+OP+ individuals, in line with data on other causes of osteoporosis, suggesting a common pattern of circulating miRNAs independent of the underlying cause.