"Vital exhaustion," characterized by fatigue, irritability, and demoralization, precedes new and recurrent coronary events. Biological mechanisms explaining this association are not fully understood. The objective was to investigate the relationship between vital exhaustion, lifestyle, and lipid profile. Vital exhaustion, smoking, body mass index (BMI), alcohol consumption, exercise capacity, and serum lipids were determined in 300 healthy women, aged 56.4 +/- 7.1 years. No statistically significant associations were found between vital exhaustion and lifestyle variables. Divided into quartiles, vital exhaustion was inversely related to high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 in a linear fashion after adjustment for age, BMI, exercise capacity, and alcohol consumption. A multivariate-adjusted vital exhaustion-score in the top quartile, as compared to one in the lowest, was associated with 12% lower HDL-C and 8% lower apolipoprotein A1 (p < .05). In conclusion, alterations in lipid metabolism may be a possible mediating mechanism between vital exhaustion and coronary heart disease. The impact of lifestyle variables was weak.