Vitamin/mineral supplements (VMS) and vitamin/mineral and/or dietary supplements (VMDS) are commonly consumed, based on the belief of their invigorating properties. Still, the association of VMS/VMDS with fatigue in the general population remains sparse and conclusions are mixed. This study aimed to understand the association between VMS/VMDS and fatigue.Two cross-sectional studies (2014-2017 and 2018-2021) conducted on a population-based cohort. Participants were divided into VMS/VMDS users and non-users. Fatigue levels were assessed using the Fatigue Severity Scale (FSS) and the 14-item version of the Chalder Fatigue Scale (CFS).Overall, 2084 (50.8 % female, 61.7 ± 9.8 years) and 1728 (51.0 % female, 64.1 ± 9.3 years) were included in the first and second surveys, respectively. In the first survey, after multivariable analysis, no association was found between VMS use and FSS: adjusted mean ± sem 3.04 ± 0.13 vs. 2.82 ± 0.03 for users and non-users, respectively, p = 0.083, while users scored higher in the CFS: 6.17 ± 0.22 vs. 5.72 ± 0.06 for users and non-users, respectively, p = 0.048. In the second survey, no association was found between VMS use and FSS (2.83 ± 0.19 vs. 2.84 ± 0.03, p = 0.952) and CFS (5.38 ± 0.33 vs. 5.61 ± 0.06, p = 0.504). In the first survey, VMDS users scored higher in both FSS (3.03 ± 0.06 vs. 2.76 ± 0.04, p < 0.001) and CFS (6.19 ± 0.11 vs. 5.58 ± 0.06, p < 0.001) while no differences were found in the second survey in both FSS (2.93 ± 0.07 vs. 2.81 ± 0.04, p = 0.161) and CFS (5.78 ± 0.12 vs. 5.54 ± 0.07, p = 0.088).In this population-based cross-sectional study, the authors found no consistent association between VMS consumption and fatigue. Participants taking VMDS tended to present with higher fatigue scores.