Background:  Post‐stroke fatigue (PSF) often occurs after stroke and has a negative impact on the rehabilitation process. Several studies focused either on short‐ or on long‐term PSF and their relations with stroke characteristics. However, possible pre‐stroke risk factors such as history of depression, pre‐existent white matter lesions or brain atrophy were usually not taken into account. Therefore, the precise mechanisms underlying PSF remain still unclear. This study was aimed at assessing the possible contributions of (pre‐)stroke factors to both short‐term PSF and its course over time.

Methods:  This study pertains to 108 patients with an acute cerebral infarction. PSF was rated by the Checklist Individual Strength at 2 months and 1.5 year post‐stroke. The relation between (pre‐)stroke factors and PSF was assessed with multivariate regression analysis.

Results:  The prevalence of baseline PSF was 35% and at follow‐up 33%. Older age had a protective effect on PSF at baseline (OR 0.95; 95% CI 0.91–0.98), whereas post‐stroke depressive symptoms and infratentorial infarctions were related to an increased risk for PSF (OR 1.40; 95% CI 1.21–1.63 and OR 4.69; 95% CI 1.03–21.47, respectively). Baseline fatigue was related to an increased risk of PSF at follow‐up (OR 1.15; 95% CI 1.09–1.22).

Conclusions:  Predictors for baseline fatigue were younger age, post‐stroke depressive symptoms, and infratentorial infarctions. Baseline fatigue did predict fatigue outcome over time, suggesting that early interventions might be useful to prevent deteriorated PSF.