Water vending is a significantly lucrative business laden with stressful and strenuous activities making it to be implicated in oxidative damage, lipid peroxidation and the susceptibility of erythrocytes to haemolysis. The study was designed to investigate the degree of erythrocyte osmotic fragility (EOF), Malondialdehyde (MDA) concentrations, Superoxide dismutase (SOD), Catalase and reduced glutathione (GSH) activities which detoxifies the superoxide radicals produced from rigorous musculoskeletal activity such as water vending among water vendors and non-water vendors. Copies of questionnaire were randomly distributed in the study area to a total of 192 subjects of which water truck pushers (experimental group) were 96 and non-water truck pusher (Control group) were also 96 individuals. 5ml of blood was obtained from the median cubital vein via venepuncture. Ethical clearance was obtained from the health research ethics committee of A.B.U, Zaria, Nigeria. 3ml of samples stored in EDTA bottles were used for EOF whereas serum samples obtained from 2ml of centrifuged blood were assayed biochemically for MDA concentration using TBARS assay and antioxidant enzymes activities. Data obtained were analysed using independent sample T-test and cross Tab for descriptive statistics. The result showed a significant (P < 0.05) increase in serum MDA concentrations of the experimental group with a value of 230.33 ± 4.75 nmol/ml compared to control group with a recorded value of 215.61 ± 3.59 nmols/mL. EOF of water vendors showed significant (P < 0.05) increase with a value of 85.83 ± 0.37% when compared to 78.69 ± 0.53% for non-water truck pushers at 0.4% concentration of NaCl solution. Significant increase in SOD activity (15.26±0.84 IU/L) among the water vendors compared to the control (11.48±1.16 IU/L). Catalase activity shows statistically significant (P < 0.05) increase in water vendors with a value of 63.33 ± 1.08 IU/L compared to the non-water vendors with corresponding value of 56.19 ± 1.66 IU/L respectively and a statistically significant decrease in GSH activity (29.15±0.14 IU/L) among the water vendors compared to the control (38.93±0.95 IU/L) was recorded. In conclusion, these findings suggest that increase exists in the EOF and MDA concentration of water vendors and a redox imbalance had occurred in the antioxidant enzymes as such the need to mitigate this effect.