The effects of hepatitis and drug use on nutritional problems in HIV infection have rarely been examined despite the importance of drug use in the global HIV pandemic. We examined the effects of HIV, hepatitis C, and drug use on serum micronutrients in 300 US Hispanic adults. Chronic hepatitis C infection was associated with lower serum retinol (-8.2 microg/dl, P < 0.0001), alpha-tocopherol (-0.10 ln microg/dl, P = 0.024), and carotenoids (-19.8 microg/dl, P < 0.0001). HIV infection was associated with lower selenium (-6.1 microg/l, P = 0.028). Elevated triglycerides in HIV infection were associated with higher serum retinol and alpha-tocopherol. Drug use was not independently associated with micronutrient alterations. We conclude that hepatitis C is an important determinant of low serum micronutrients, and should be considered in any nutritional assessment of HIV infected populations. As the safety of micronutrient supplementation is not established, policy for appropriate HIV clinical care should distinguish between populations with and without hepatitis coinfection.