Abstarct: Background and Aim: Considering the increasing prevalence of overweight and sedentary lifestyle, which is associated with higher respiratory sensitivity and relative mucosal immune deficiency, studying the acute changes in salivary immunoglobulin A and pulmonary function in response to a single session of high-intensity interval exercise can provide valuable information about the level of stress tolerance and potential risks of this type of activity in inactive men. The aim of this study was to investigate the effect of high-intensity interval exercise (HIIE) on salivary immunoglobulin A (sIgA) and pulmonary function (FEV1, FVC, and PEF) in overweight, physically inactive men. Methods: The present study was quasi-experimental and applied in terms of purpose. The statistical population consisted of overweight men (body mass index 25 to 29.9 kg/m²) aged 30 to 40 years in Shahroud. Among them, 18 individuals were purposefully selected baxsed on inclusion and exclusion criteria and entered the study after completing the informed consent form, and were randomly assigned to two groups: high-intensity interval training (9 individuals) and control (9 individuals). The HIIT protocol consisted of 5 minutes of warm-up, 8 bouts of 1-minute activity at 85–90% of maximum heart rate, and 5 minutes of cool-down. The control group rested in a seated position for the same duration. baxseline measurements included height, weight, blood pressure, waist circumference and hip circumference, and body mass index (BMI) calculation. Saliva samples were collected before and immediately after the intervention to measure immunoglobulin A. Pulmonary function (FEV1, FVC, and PEF) was also measured at both time points. Data were analyzed using repeated-measures analysis of variance at a significance level of P < 0.05. Results: The results showed that one session of high-intensity interval exercise (HIIE) led to a significant decrease in salivary immunoglobulin A (sIgA) levels (P < 0.001; 54% reduction), while the decrease in the control group was significantly smaller. Also, FVC (P < 0.001; approximately 4.8% increase) and FEV1 (P = 0.001; approximately 6.3% increase) significantly increased in the exercise group, but no significant changes were observed in the control group. However, the increase in PEF in the exercise group (approximately 10%) was not statistically significant (P = 0.055). Conclusion: A single session of high-intensity interval exercise in overweight, inactive men simultaneously causes a temporary reduction in mucosal immunity (sIgA) and acute improvement in some pulmonary function indices (FVC and FEV1). These findings emphasize the need for attention to immune recovery periods while also taking advantage of the beneficial respiratory effects of this type of exercise.