The study investigated the effect of a 12-week High Intensity Interval Training (HIIT) on Serum Brain Derived Neurotrophic Factor (BDNF) among obese undergraduates of the University of Benin. The pretest-posttest randomized experimental design was employed for the study. The study involved a population of one hundred and twenty obese undergraduates, with a sample of twenty-four selected using simple random sampling. The participants’ anthropometric profiles were analyzed descriptively using mean and standard deviation, and the hypothesis was tested using analysis of covariance (ANCOVA) with statistical significance set at a p-value of <0.05. The Bonferroni post-hoc test was conducted to pinpoint the source of the differences between the groups. The results showed a significantly higher increase in Serum BDNF levels (2.07 ± 1.9 vs. 2.38 ± 2.1) in the experimental group. This suggests that the HIIT protocol had a notable impact on the serum BDNF concentration of the obese undergraduates. Therefore, HIIT may serve as an effective intervention for elevating BDNF levels and potentially enhancing brain health. The study recommends that policymakers in Nigeria and other sub-Saharan African nations should prioritize addressing obesity due to its potential cognitive complications.