© 2018, © 2018 Central Institute for Labour Protection–National Research Institute (CIOP-PIB). Background. This study aimed to evaluate the physiological strain index (PSI) along with specific immune system markers in response to a simulated firefighting occupation workload. Methods. Ten healthy male adults completed a 6-min simulated fire stair climb (SFSC) at 60 steps/min. The protocol consisted of four conditions, some including wearing a 34.04-kg vest to simulate personal protective equipment (PPE) and/or inclusion of a color-word interference test (CWIT) as a distracting mechanism. The PSI was evaluated by continuously monitoring the heart rate and core temperature. Salivary cortisol (CORT) was measured at baseline, mid SFSC and post SFSC. C-reactive protein (CRP) was evaluated at baseline and 1 h post SFSC. Results. Repeated-measures analysis of variance showed a significantly different PSI across conditions (p = 0.001). A significantly elevated PSI was exhibited during all 6 min of SFSC for both PPE and PPE + CWIT conditions. Neither CORT (p = 0.116) nor CRP (p = 0.700) was significantly different across conditions or from baseline. Conclusion. These findings suggest that firefighters are potentially at a substantial degree of physiological stress from exercise and the weight of gear alone. Further work should be conducted to further evaluate the usefulness of the PSI as a means to monitor firefighters during fire suppression.