Resting energy expenditure (REE) and body composition were investigated in 60 clinically stable patients with human immunodeficiency virus (HIV) infection varying with respect to immune impairment. REEs differed significantly from predicted values (≶10% of the Harris-Benedict [HB] equation) in 40% of patients. Seven percent of patients showed markedly increased REE (>+20% of HB prediction), whereas REE was decreased in 13% (<−10%). Increased REE was found during all clinical stages of the disease (Walter Reed [WR] 2 through 6) and was not strictly associated with the degree of immune impairment, presence of diarrhea or Kaposi's sarcoma, nutritional state, or anamnestic wasting. Twenty-seven patients were evaluated for a mean period of 319 days; 11 lost more than 5% of their initial body weight during the observation period. Weight-losing patients were normometabolic before but showed a significantly increased REE (+7% of predicted values or +8% when compared with previous measurements) during weight loss. The degree of deviation from estimated REE was strongly associated with the degree of weight loss. We summarize that increased REE is not a constant feature of HIV infection. It is not associated with clinical and laboratory parameters of immune deficiency, but may occur during weight loss. Thus increased REE represents an inadequate adaptation to malnutrition and contributes to wasting.