We examined the effect of acute moderate- to high-intensity resistance exercise on feelings of energy and fatigue in sedentary college women reporting a persistent above-average frequency of fatigue. Fourteen sedentary female volunteers reporting persistent fatigue completed three counterbalanced conditions [70% one-repetition maximum (1-RM), 15% 1-RM/placebo, and a no-exercise control]. In the exercise conditions, participants performed four sets of 10 repetitions of three lower-body resistance exercises. The Profile of Mood States-Brief Form (POMS-B) vigour and fatigue mood scores were obtained immediately before conditions, every 11 min and 40 s during conditions, and 20 and 30 min after conditions. The data showed a significant main effect for vigour (P = 0.01). Vigour scores were significantly higher for the 70% 1-RM than the control condition (P = 0.01). No significant difference was observed between the 70% 1-RM and 15% 1-RM/placebo conditions. There was a significant main effect for fatigue (P = 0.04). Fatigue scores were significantly lower for the 15% 1-RM/placebo than the control condition (P = 0.04). Acute moderate- to high-intensity lower-body resistance exercise increased feelings of energy during and after exercise compared with the control. It is unclear whether this effect is a placebo effect because, while it did not differ from the placebo condition, we cannot rule out that resistance exercise at a wide range of intensities produces increased feelings of energy.