Background <p>Nurses experience physiological and cognitive challenges in high-temperature hospitals while wearing full-body Personal Protective Equipment (PPE). Identifying solutions is crucial for their well-being and performance. The aim of this study was to assess the effects of integrating cooling vests into full-body PPE on physiological and cognitive markers among hospital nurses in Iran.</p> Methods <p>Forty nurses from Shiraz, Iran, participated, with 20 participants in the control group and 20 participants in the intervention group. The control group wore standard PPE, while the intervention group used cooling vests with their PPE. Objective evaluations included physiological measurements and cognitive function tests, while subjective evaluations assessed fatigue, thermal sensation, thirst, and moisture.</p> Results <p>Physiological measurements, including heart rate maximum, and energy expenditure, showed no notable differences between the two groups. The effect of the cooling vest in the Continuous Performance Test (CPT) in comparison between the two groups decreased the response time (<i>p</i> &lt; 0.001). The N-Back test, no response (<i>p</i> = 0.189), and response time (<i>p</i> = 0.871) between the two groups showed no significant difference. Subjective parameters were considerable reduced in the intervention group (<i>p</i> &lt; 0.001).</p> Conclusion <p>Integrating cooling vests into PPE may alleviate physiological and cognitive challenges nurses experience in high-temperature environments, emphasizing the importance of providing appropriate PPE and cooling solutions for healthcare professionals working in hot conditions.</p> Clinical trial number <p>Not applicable.</p>