Essential hypertension is one of the most prevalent non-communicable diseases in sub-Saharan Africa and elsewhere in people of sub-Saharan origin. This study investigated the role of nitric oxide (NO) and glucose 6-phosphate dehydrogenase (G6PD) activity in aetiology of essential hypertension. An analytical cross-sectional design was applied to 89 essential hypertensive participants and 89 healthy normotensive participants, making a total of 178. Blood was collected for G6PD activity and serum levels of nitric oxide, glucose, creatinine, urea and electrolytes. Analysis of variance was employed to establish whether there was a difference in mean levels of NO between those that were G6PD deficient and those who were not. Lower NO levels were observed in those who were G6PD deficient though the difference was not statistically significant. A logistic regression was used to investigate the association of age, sex, NO levels, and G6PD deficiency with essential hypertension as the dependant variable. It was established that with an increase in NO levels there was less likelihood of developing hypertension (odd ratio (OR)=0.99), whereas individuals with impaired G6PD activity were 2.9 times more likely to develop hypertension than those with normal activity (OR=2.9). Our conclusion was that NO is important in prevention of hypertension through its vasodilator effect on arterioles.