Fatigue is one of the most frequent symptoms in post-COVID syndrome (PCS) patients and describes along-term feeling of tiredness and exhaustion. Frequently, it follows an infection or is a component of depressive symptoms. But fatigue itself is also arisk to mental health like other chronic conditions. The objective of this paper was to analyse the relationship between fatigue and depression/anxiety and the differences between PCS patients and fully recovered COVID-19cases. In alongitudinal study with three measurement points, insured members of the Statutory Accident Insurance and Prevention in the Health and Welfare Service with aSARS-CoV‑2 infection in 2020 were asked about fatigue, depression/anxiety and persisting COVID-19symptoms. To analyse the longitudinal effects of the two variables, across-lagged panel model was applied. In the present sample (n = 860), aproportion of 68.7% to 75.1% of people was suffering from PCS. The results showed amodel fit of R2 = 61.49% and all effects were significant, but the cross-lagged effects were not significantly different from each other. If stratified according to whether PCS symptoms were present, the cross-lagged effects weakened in both groups, while the effects of fatigue on depression and anxiety only remained in the group of those affected by PCS. The results show arelationship in both directions between fatigue and depression/anxiety. PCS patients can benefit from psychotherapeutic treatment to tackle fatigue and prevent depression and anxiety.