Background: Overweight and obesity have been associated with cardiovascular disease, diabetes mellitus type 2, osteoarthritis, respiratory disorders, cancer, and decline in life expectancy. Elevation in pro-inflammatory cytokine has been associated with decline in metabolic function and the rise in various diseases risk factors. C-reactive protein which is synthesized at the liver has been used to evaluate low-grade risk systemic inflammation. High-intensity Interval Training (HIIT) have been developed as an alternative exercise with low volume and expected to help efficiently reduce risk factors associated with the overweight condition. Objective: To evaluate the effect of the HIIT exercise program for 4 weeks on hsCRP serum level in overweight men in Medical Rehabilitation Outpatient Clinic at dr. Soetomo Hospital. Methods: This study was conducted from January-March 2021. Eighteen men visited Medical Rehabilitation Outpatient Clinic at dr. Soetomo Hospital recruited and randomized into the control and exercise groups. The exercise group performed the HIIT exercise program for 4 weeks while the control group received no intervention. Peripheral blood samples for serum hsCRP were collected at baseline and 30 minutes post training at the first and the last exercise in the exercise group. Results: Within-group comparison in exercise and control group; and between group comparison of serum baseline hsCRP levels, showed no significant difference (p = 0,176, p = 0,09, and p = 0,04, respectively). Within-group acute hsCRP levels showed no significant difference (p=0,163). Conclusion: The HIIT exercise program for 4 weeks showed no significant effect on serum hsCRP levels in overweight men.