Background & objective: This study aims to assess the effect of cooling helmet during surgery on neuron specific enolase (NSE) and delirium levels following open heart surgery patients with cardiopulmonary bypass (CPB) using a heart-lung machine. Methodology: This double-blind randomized clinical trial took place from October to December 2021 in a tertiary care hospital. The research used a modified cooling helmet to decrease brain temperature. Inclusion criteria were adult patients who were scheduled for open heart surgery with CPB. The subjects were randomized into two groups: patients with the cooling helmet on as the treatment group (n = 12) and the patients with the non-cooling helmet on as the control group (n = 13). The differences between NSE and delirium levels in both groups were assessed at specific times. Results: NSE levels in the treatment group were lower than the control group (7.13 ± 7.63 vs. 12.49 ± 6.81; P < 0.05). Regarding the delirium, no statistically significant difference was found in both groups (P > 0.05). Conclusion: The hypothermia effect of the cooling helmet is associated with a decrease of neuron specific enolase levels, but it did not significantly correlate to prevent the delirium after open heart surgery patients with the cardiopulmonary bypass machine. © 2022 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.