activity (EDA) while breathing elevated PO2 in the hyperbaric environment (HBO2) as a possible means to predict impending CNS-OT. To this end, we used machine learning to automatically detect and predict the onset of symptoms associated with CNS-OT in humans by using features derived from EDA in both time and frequency domains. Methods: We collected electrodermal activity (EDA) data from forty-nine exposures to HBO2 while subjects were undergoing cognitive load and exercise in a hyperbaric oxygen chamber. Four independent experts were present during the experiment to monitor and classify any symptoms associated with hyperbaric oxygen toxicity. We computed a highly sensitive time varying spectral EDA index, named TVSymp, and extracted informative features from skin conductance responses (SCRs). Machine learning algorithms were trained and validated for classifying features from SCRs and TVSymp as CNS-OT related or non-CNS-OT related. Machine learning models were validated using a subject-independent leave one subject out (LOSO) validation scheme. Results: Our machine learning model was able to classify EDA dynamics related to CNS-OT with 100 % sensitivity and 84 % specificity via LOSO validation. Moreover, the median prediction time for CNS-OT symptoms was ~ 250 s preceding the occurrence of actual symptoms. Significance: This study shows that EDA can potentially be used for early prediction of CNS-OT in divers with a high sensitivity and sufficient prediction time for countermeasures. While the study results are promising, independent validation datasets are warranted to confirm the findings. However, the current results are well corroborated in an animal study, which consistently showed seizure prediction time of 2 min prior to seizure.