OBJECTIVE The present study evaluated whether chronic stress levels moderated the impact of laboratory stressors on subjective and behavioral responses to alcohol. METHODS Healthy volunteers (N = 60; 30 male) completed measures of background stress levels (e.g., major life events). In addition, subjects were exposed to two laboratory stressors (i.e., cold pressor or film stressor task) or a control condition after consuming a 0.7 g/kg dose of alcohol. RESULTS Regression analyses showed that the combination of high background stress levels and exposure to a lab stressor reduced two measures of perceived intoxication (i.e., Sensation Scale, Visual Analog Intoxication Scale). CONCLUSIONS These data are consistent with a biobehavioral model of alcohol use where acute and chronic stressors are associated with a diminished response to alcohol. The possible mechanisms that may underlie this sobering effect include stress-related cognitive deficits and situation specific tolerance associated with high chronic stress levels.