This study aimed to investigate the changes in physical fitness and patient-reported outcomes as well as the correlation between these two factors in adult patients with newly diagnosed acute leukemia during chemotherapy. This was a longitudinal observational study. Patients were recruited from a tertiary hospital in China with a follow-up period of less than 90 days. Physical fitness was assessed using body mass index (BMI), mean skinfold thickness, waist-to-hip ratio, spirometry, mean grip strength, and flexibility at T1 (before chemotherapy), T2 (7-14 days after initial chemotherapy), and T3 (completely relieved or after two chemotherapy courses). A repeated-measures analysis of variance was used to analyze the physical fitness changes during follow-up. Multiple linear regression was used to analyze the factors influencing patient-reported outcomes. The study analyzed 121 patients. Changes in physical fitness during chemotherapy, including BMI, mean skinfold thickness, lung capacity and flexibility were not all equal at all three time points (F = 38.477, P <
0.001
F = 44.506, P <
0.001
F = 70.948, P <
0.001
and F = 70.965, P <
0.001), and post-hoc tests showed that they all trended to be decreasing before they were elevated (T2 <
T3 <
T1). The waist-to-hip ratio decreased and then increased (F = 12.138, P <
0.001,T2 <
T3 = T1) and the mean grip strength remained stable (F = 0.137, P = 0.718). The total patient-reported outcome scale score decreased and subsequently increased (F = 362.507, P <
0.001,T2 <
T1 <
T3). BMI, mean skinfold thickness, spirometry, and flexibility influenced the patient-reported outcomes (B = 1.427,P <
0.001
B=-15.340,P <
0.001
B = 0.002,P = 0.014
B = 0.249,P <
0.001). Physical fitness affects patient-reported outcomes in those with acute leukemia. During chemotherapy, especially myelosuppression, healthcare providers should monitor patients' physical fitness and implement positive patient-appropriate interventions, such as exercise interventions, to promote better outcomes.