Increased concentrations of tau protein are associated with medical conditions involving the central nervous system, such as Alzheimer's disease, traumatic brain injury and hypoxia. Diving, by way of an elevated ambient pressure, can affect the nervous system, however it is not known whether it causes a rise in tau protein levels in serum. A prospective observational pilot study was performed to investigate changes in tau protein concentrations in serum after diving and also determine their relationship, if any, to the amount of inert gas bubbling in the venous blood. Methods: Subjects were 10 navy divers performing one or two dives per day, increasing in depth, over four days. Maximum dive depths ranged from 52-90 metres' sea water (msw). Air or trimix (nitrogen/oxygen/helium) was used as the breathing gas and the oxygen partial pressure did not exceed 160 kPa. Blood samples taken before the first and after the last dives were analyzed. Divers were monitored for the presence of venous gas emboli (VGE) at 10 to 15 minute intervals for up to 120 minutes using precordial Doppler ultrasound. Results: Median tau protein before diving was 0.200 pg•mL-1 (range 0.100 to 1.10 pg•mL-1) and after diving was 0.450 pg•mL-1 (range 0.100 to 1.20 pg•mL-1 ; P = 0.016). Glial fibrillary acidic protein and neurofilament light protein concentrations analyzed in the same assay did not change after diving. No correlation was found between serum tau protein concentration and the amount of VGE. Conclusion: Repeated diving to between 52-90 msw is associated with a statistically significant increase in serum tau protein concentration, which could indicate neuronal stress.