Although survival has improved among patients with acute leukemia, there is still a considerable risk of severe complications throughout the course of treatment. This contrast increases the interest in monitoring health related quality of life (HRQOL) in these patients. This study presents a longitudinal HRQOL evaluation (European Organisation for Research and Treatment of Cancer core 30-item questionnaire; EORTC-QLQ C-30) and the impact of infectious comorbidity among 60 patients with leukemia (median age 47) treated in an outpatient management program at Copenhagen University Hospital. Significant improvement was seen on several HRQOL scores during follow-up. Explorative general linear models (GLMs) suggest that high cumulative severity of infectious comorbidity significantly reduces physical functioning and overall quality of life at treatment completion.