One commonly used instrument for evaluating general health and functional status is the medical outcomes survey short form 36 (MOS). Scores obtained from this instrument are known to vary with chronic diseases and depression. However, the degree to which these health dimensions may be influenced by sleep quality or sleepiness is not well understood. A cross-sectional study was performed on the association between general health status, as determined by the MOS, with sleepiness, assessed using a standardized questionnaire [the Epworth sleepiness scale (ESS)] and the multiple sleep latency test (MSLT). One hundred twenty-nine subjects (68 women), aged 25–65 years, without severe chronic medical or psychiatric illnesses, underwent an overnight sleep study, followed by an MSLT (consisting of a series of four attempts at napping at 2-hour intervals), and completed the MOS and the ESS. The mean MSLT score was 11 ± 2 minutes, (range 2–20) and the mean ESS score was 10 ± 5 (range 0–24). Scores for the MOS dimensions “general health perceptions”, “energy/fatigue”, and “role limitations due to emotional problems” were correlated significantly with ESS scores (r = −0.30, −0.41, and −0.30, respectively; p values were all <0.001). The MSLT was also significantly correlated with “energy/fatigue” (r = −0.19; p < 0.05). After considering the effects of chronic illness and/or body mass index in a multiple hierarchical regression analysis, sleepiness, as assessed by the ESS score, explained 8% of the variance in general health perceptions, 17% of the variance in energy/fatigue, 6% of the variance in the summary measure of well-being, and 3% of the variance in the summary measure of functional status. The variation of MOS scores with sleepiness, unrelated to age or chronic disease, suggests that measures of general health status may be broadly influenced by sleepiness and sleep quality. These data suggest that 1) sleepiness has an important impact on general health and functional status, specifically influencing self-perceptions regarding energy/fatigue; 2) a more .specific assessment of sleepiness in general health evaluations may help explain some of the observed variability in these measures across subjects; and 3) general health measures may be useful in the evaluations of patients with sleep disorders.