Background: Fatigue is associated with multidimensional factors in heart failure patients. Investigating longitudinal changes in fatigue and its association in patients undergoing cardiac surgery is needed to create interventions for improving fatigue during recovery. Aims: This study examined the trajectory of fatigue and its associated factors over time in patients undergoing cardiac surgery. Methods: This longitudinal study enrolled 125 patients undergoing cardiac surgery in northern Taiwan. Patients completed questionnaires before surgery, at discharge, and at 1, 3 and 6 months post-discharge. Fatigue was measured using the General Fatigue Scale. Generalised estimating equation models were fitted to identify variables associated with fatigue over time. This study complied with the STROBE checklist. Results: The sample (mean age = 60.70 ± 10.42) was mostly male (68%). High fatigue was found in 73.6% of patients before cardiac surgery and significantly decreased over the six months after discharge. NYHA III/IV, lower haemoglobin level, more symptom distress, poor sleep quality, higher anxiety and depression and lower social and family support were significantly associated with an increase in fatigue levels over time. Compared with before discharge, decreases in sleep quality at 1, 3 and 6 months were significantly associated with an increase in fatigue levels (p <.001). The increases in social support (B = 0.20, p =.016) and family support (B = 0.37, p =.002) at 6 months were significantly associated with an increase in the fatigue scores. Conclusion: Fatigue was common and associated with symptoms, sleep quality, emotion and social support in patients undergoing cardiac surgery. In addition to symptom management, improving sleep quality and social support are important to manage fatigue for the long-term care of patients undergoing cardiac surgery. Relevance to clinical practice: Patient education on symptom management, sleep hygiene and family support is suggested to improve fatigue in patients recovering from cardiac surgery.