Acute myeloid leukemia (AML) is associated with poor survival. While clinical prognostic factors of survival have been identified, the contribution of patient-reported symptoms has only received marginal attention. Fatigue is one of the most commonly reported symptoms of AML. There is some evidence that fatigue is associated with shorter survival in hematological malignancies. However, the prognostic effects of fatigue in a homogenous cohort of patients with untreated AML has not been tested. We here report results of a prospective study on the prognostic value of patient-reported fatigue prior to onset of treatment, for 2-year survival in 94 AML patients. Cox regression models controlling for demographic and clinical factors showed that those with severe fatigue (22%) had decreased survival rates (Hr = 2.255, 95% CI = 1.16-5.60, p = 0.019). Further exploration showed that fatigue was associated with increased plasma concentrations of IL-6 and TNF-α, but not with demographic or disease-related factors. In conclusion, we here show for the first time that the experience of severe fatigue prior to remission induction chemotherapy (IC) is prognostic for shorter survival in patients with AML of all ages. These findings point to the importance of interventions aimed at relieving fatigue especially before or in the early phases of treatment in order to improve survival.