Speech production in aphasia is often described as “effortful”, though the consequences of consistent, high degrees of cognitive effort have not been explored. Using recent work on mental effort as a theoretical framework, the present study examined how effort-related fatigue produces decrements in performance in picture naming among participants with post-stroke aphasia. We analyzed three data sets from prior studies where participants completed a large picture naming test. Decreasing naming accuracy across trials was statistically significant in two of the three samples. There were also significant effects of practice (better performance on a second test administration), word frequency (better performance for more frequent words), and word length (better performance for shorter words). These results are the first concrete demonstration of fatigue affecting performance on a language task in post-stroke aphasia. They open a new avenue for research on mental effort/fatigue with potential implications for aphasia assessment, treatment, and management.