Background and Purpose. Stroke is the leading cause of adult disability. Rehabilitation is a vital component of post-stroke care with two-thirds of survivors requiring rehabilitation. Fatigue is a common issue affecting stroke patients and is a barrier to rehabilitation causing inefficient care provision and potential limitation to patient recovery. No study to date has investigated whether the experience of fatigue is different between the two main causes of ischemic stroke: small-vessel (SVD) and large-vessel disease (LVD). The aim of the present study is to complete a pilot study to inform the feasibility, design, magnitude of difference in experience of fatigue, and sample size for a definitive study to evaluate differences in fatigue between these two groups of stroke patients. The experimental hypothesis is that participants with LVD experience a significantly greater level of fatigue than those with SVD as assessed by the Fatigue Severity Scale (FSS). Methods. The study used a cohort observational design. Thirteen participants were recruited over a two-month period from King's College Hospital. Participants were visited on average at the start of the second week of rehabilitation to complete the FSS. An independent t-test and ANCOVA were performed. For all statistical analyses, a significance level of p < 0.05 was used. Results. The study demonstrated a trend towards LVD participants reporting higher fatigue scores than SVD participants, even when controlling for age, with gender having no confounding effect. Conclusions. Fatigue is common amongst ischemic stroke rehabilitation participants with 85% of the combined sample experiencing fatigue at the start of the second week. The results demonstrate a trend towards LVD participants experiencing greater fatigue. While the results were non-significant, the study demonstrates a feasible methodology which could help lay the groundwork for future research. Copyright © 2010 John Wiley & Sons, Ltd.