Physical activity (PA) can improve sleep quality, low energy, and fatigue. Though poor sleep quality may induce feelings of low energy and fatigue, the potential moderating effect of sleep quality on associations between PA and feelings of energy and fatigue among adolescents is unknown. Thus, this study examined the moderating effect of sleep quality on associations between PA frequency and feelings of energy and fatigue among adolescents in Ireland. Adolescents (N = 481; 281 males, 200 females) aged 15.1 ± 1.7 years self-reported PA frequency, feelings of energy and fatigue, and sleep quality (September to December 2015). Two-way ANCOVAs examined variation in feelings of energy and fatigue according to the interaction of PA and sleep quality. Standardized mean difference (d) quantified the magnitude of differences. Poor sleepers with low PA reported greater feelings of fatigue compared to normal sleepers with low PA (d = 1.02; 95% CI 0.60, 1.44), and poor sleepers with moderate PA reported greater feelings of fatigue compared to normal sleepers with moderate PA (d = 0.50; 0.17, 0.82). Poor sleepers with low PA reported greater feelings of fatigue compared to both poor sleepers with moderate PA (d = 0.44; 0.05, 0.83) and poor sleepers with high PA (d = 0.87; 0.46, 1.28). Poor sleepers with moderate PA reported greater feelings of fatigue compared to poor sleepers with high PA (d = 0.52; 0.14, 0.91). Poor sleep did not moderate the association between PA and feelings of energy. Sleep quality moderates the association between PA frequency and feelings of fatigue. Fatigue symptoms improve as PA frequency increases among adolescents with poor sleep quality.