The COVID-19 pandemic significantly impacted health-related quality of life (HRQoL) among adolescents, with declines in physical activity (PA) and fitness (PF), partly due to school closures. Physical education (PE) in schools plays a crucial role in promoting well-being and PA. Research suggests gender differences in PA and PF and also in responses to PE. A total of 176 adolescents (48.3% girls; mean age 15.6 ± 0.6) reported gender, age, weekly PA, HRQoL (Kidscreen-10), and enjoyment in PE (FEFS-J: pleasure, flow, recovery). PF was assessed using the German motor performance test 6-18. Results showed that girls had significantly lower HRQoL and enjoyment in PE scores than boys, but not in PA or PF. Significant positive correlations between HRQoL and all 3 dimensions of PE enjoyment were found in girls (r[subscript s]= 0.31 - 0.54), while in boys, only pleasure showed a significant correlation with HRQoL (r[subscript s] = 0.32). Multiple regression analyses showed that pleasure in PE was positively associated with HRQoL for both girls ([beta] = 0.49; R[superscript 2] = 0.30) and boys ([beta] = 0.52; R[superscript 2] = 0.09). In conclusion, the results highlight the importance of enjoyment in PE for HRQoL in both genders. Teachers should adapt their planned activities to consider the different ways in which boys and girls enjoy PE.