Fatigue is a common symptom in patients with Lyme disease. The purpose of this study was to characterize fatigue in untreated adult patients presenting with erythema migrans. Selected variables were assessed to determine if any correlated with the presence or severity of fatigue. Fatigue was assessed on the day of the evaluation by a Visual Analogue Scale (VAS), over the past 14days by the 11-item Fatigue Severity Scale (FSS-11) and over the past 28days based on a question from the 36-item Short Form General Health Survey version 2. Fifty-one patients with erythema migrans whose mean age was 49.8years, and 33 (64.7%) of whom were male, were evaluated in this study. The 3 measures of fatigue were positively correlated with one another (P≤0.01). Twenty-six (51%) had fatigue based on a VAS score above 0. Ten (19.6%) had severe fatigue based on an FSS-11 score of ≥4. The strongest correlate for higher fatigue scores was having a greater total number of symptoms. Based on the FSS-11 assessment tool, approximately 20% of early Lyme patients have severe fatigue. Having a high total number of symptoms was associated with both the presence and severity of fatigue. Because prior studies have demonstrated the presence of elevated levels of proinflammatory cytokines and other molecules in the serum of highly symptomatic patients with erythema migrans, the symptom of fatigue in early Lyme disease may be a component of what has been referred to as the acute sickness response.