Study population: We examined the relationship between chronic fatigue syndrome (CFS) and allostatic load in a population-based, case–control study of 43 CFS patients and 60 nonfatigued, healthy controls from Wichita, KS, USA. Methods: An allostatic load index was computed for all study participants using available laboratory and clinical data, according to a standard algorithm for allostatic load. Logistic regression analysis was used to compute odds ratios (ORs) as estimates of relative risk in models that included adjustment for matching factors and education; 95% confidence intervals (CIs) were computed to estimate the precision of the ORs. Results: CFS patients were 1.9-times more likely to have a high allostatic load index than controls (95% CI = 0.75, 4.75) after adjusting for education level, in addition to matching factors. The strength of this association increased in a linear trend across categories of low, medium and high levels of allostatic load (p = 0.06). Conclusion: CFS was associated with a high level of allostatic load. The three allostatic load components that best discriminated cases from controls were waist:hip ratio, aldosterone and urinary cortisol.