Advanced HIV infection combined with undernutrition and antiretroviral therapy (ART) places HIV/AIDS patients at high risk of electrolyte abnormalities and increased morbidity and mortality. Here, in a sub-study of a large published randomized trial, we evaluated if nutritional supplements will help curtail renal electrolyte loss in HIV/AIDS patients starting ART. 130 malnourished HIV-positive patients referred for ART received lipid-based nutrient supplements alone (LNS, n = 63) or together with vitamins and minerals (LNS-VM, n = 67). Serum and spot urine samples were collected and assayed for creatinine, potassium, magnesium and phosphate concentrations at baseline and after 12 weeks of ART, and fractional excretion and reabsorption were calculated using standard equations. Eighteen (28.6%) patients from the LNS and 16 (23.9%) from LNS-VM groups died, most during the referral interval before starting ART. Phosphate excretion at baseline, was high in both LNS (mean ± SD: 1.2 ± 0.6 mg/mg creatinine) and LNS-VM (1.1 ± 0.8 mg/mg creatinine) groups relative to normal physiological ranges. Phosphate excretion remained high in the LNS group (1.1 ± 0.41 mg/mg creatinine) but significantly decreased in the LNS-VM group (0.6 ± 0.28 mg/mg creatinine; p < 0.001) after 12 weeks of ART. This difference is probably explained by increased renal tubular reabsorption of phosphate in the LNS-VM group (88.3 ± 5.7%) compared to the LNS group (76.6 ± 8.9%). The fractional excretion of potassium (FEK) was not significantly different at baseline between the two groups (p = 0.69) but the values were above normal physiological ranges (i.e. >6.4%) reflecting renal potassium wasting. However, FEK was significantly lowered in the LNS-VM group (6.2 ± 3.4%) but not in the LNS group (12.8 ± 4.7%) after 12 weeks of ART (p < 0.001). Finally, the fractional excretion of magnesium was not significantly different between the two groups at baseline (p = 0.68) and remained unchanged within normal physiological ranges at 12 weeks of ART (p = 0.82) in both groups. The LNS-VM regimen appeared to offer protection against phosphate and potassium loss during HIV/AIDS treatment. This offers potential opportunities to improve care and support of poorly nourished HIV-infected patients in resource-limited settings. www.pactr.org ID number: PACTR201106000300631.