Abstract Background Fatigue negatively influences health-related quality of life. It is questionable whether fatigue is sufficiently covered by the EQ-5D. This study investigated whether fatigue is covered by the existing domains of the EQ-5D. Methods A Dutch general population sample completed the EQ-5D (3L and 5L version) and the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), of which the fatigue item was used. Outcomes were compared between participants with and without a chronic health condition. Convergent validity was assessed, and multivariate regression analyses was used to predict the RPQ fatigue item from the EQ-5D-3L and EQ-5D-5L domains separately. Results 3027 people completed the survey, of whom 52% had ≥ 1 chronic health condition. Fatigue was reported by 48% of the participants. Fatigue was moderately correlated to the EQ-5D domains ‘pain/discomfort’, ‘usual activities’, and ‘anxiety/depression’ for the 3L (r = 0.379–0.426) and 5L version (r = 0.411–0.469). For the 5L, also a moderate correlation with ‘mobility’ (r = 0.335) was observed. The remaining correlations were weak. All EQ-5D-3L and 5L domains except for ‘mobility’ were significantly associated with the RPQ fatigue item (unstandardized Beta = − 0.20–0.67; p < 0.01 to p = 0.04). Comparable outcomes were found for participants with and without ≥ 1 chronic health condition. Conclusions The extent to which fatigue is covered by the EQ-5D domains is small to moderate, with the EQ-5D-5L being slightly more sensitive to capture fatigue compared to the EQ-5D-3L. An extra fatigue item for the EQ-5D may add value, as fatigue is not fully captured by the existing domains, both in people with and without a chronic health condition.