The heat shock protein 72 (HSP72) response following exercise is well documented, however, little is known on whether the expression may be mediated by the ingestion of ergogenic aids prior to performance. The purpose of this research was to investigate the effect of sodium bicarbonate (NaHCO3) ingestion on monocyte and lymphocyte expressed HSP72 and oxidative stress for 4-h post exercise. Seven active males (22.3 ± 2.9 years, 181.6 ± 4.5 cm, 78.1 ± 8.1 kg) performed a 4-min ‘all-out’ cycle test following a dose of 0.3 g kg−1 body mass of NaHCO3, or an equimolar placebo dose of sodium chloride. HSP72 was measured by flow cytometry and oxidative stress was determined via plasma thiobarbituric acid substances (TBARS) analysis. The NaHCO3 ingestion significantly increased blood pH (p < 0.001), bicarbonate (p < 0.001) and base excess (p < 0.001) pre-exercise. Despite this there was no evidence of a significantly improved exercise performance when compared with the placebo trials (p ≥ 0.26) (means ± SD; average power 292 ± 43 W vs. 291 ± 50 W; peak power 770 ± 218 W vs. 775 ± 211 W; work completed 71 ± 10 kJ vs. 68 ± 10 kJ). Monocyte expressed HSP72 was significantly lower under experimental conditions during the 4-h post-exercise (p = 0.013), as was plasma TBARS (p < 0.001). These findings suggest that pre-exercise alkalosis can attenuate the stress response to a single bout of anaerobic exercise.