Purpose: The purpose of this study was to examine the effects of the laughter therapy program on perceived stress and psycho-neuro-endocrine-immune responses in obese women. Methods: A nonequivalent control group with a pretest-posttest design was used. The participants(n=60), whose age ranged from 30 to 50 years (pre-menopausal and body mass index of over 25 kg/m2), were assigned to the experimental group (n=24) or control group (n=26). The experimental group was provided with the laughter therapy program (12 sessions) for 6 weeks. Results: There were significant differences in perceived stress, psychological stress response, fasting blood sugar, interleukin-6, and tumor necrosis factor alpha between the two groups after the program. However, there were no significant differences in normalized low frequency (norm LF), normalized high frequency (norm HF), LF/HF ratio, and cortisol between the two groups after the program. Conclusion: It was found that the laughter therapy program had positive effects on some variables in terms of perceived stress and psycho-neuro-endocrine-immuno responses. It is suggested that the laughter therapy in this study can provide the direction for developing a program for obese women.