Stress experienced by astronauts during high-level hazardous situations may poses risk to personnel wellbeing and to mission success. Stress inoculation training (SIT) provides individuals with experience of minor stressors and coping skills during non-critical times to enhance their resistance to stress. This study evaluates the effect of exposure to a low level stressor on physiological response and cognitive load in high level stressor setting. Simulation of fire emergency on the International Space Station (ISS) in a full-scale, immersive, interactive, 3D virtual reality environment facilitated a process for stress inoculation. The experimental settings included two groups that have been exposed to either virtual no-smoke or to virtual light-smoke conditions. The two groups then experienced a subsequent stress exposure in a later trail to heavy-smoke conditions. Physiological responses and cognitive load measure were collected during the trials. The results indicated weak differences in physiological responses between the two groups, in the heavy smoke conditions. Overall, no significant differences have been detected on cognitive load categories according to NASA TLX.