Some identified setbacks of the legitimate and illegitimate explorations/exploitations of crude oil and its derivatives in the Niger Delta are degraded environment, weak economy, and deteriorating health of the populace. Therefore, the current study evaluated the effect of artisanal refinery operation on respiratory blood gases and renal functions of its workers in Rivers State. As a cross-sectional investigation with sparse population, the multistage sampling technique (including purposive and snowball tools) was adopted to recruit 203 (including 120 operators of artisanal refinery―OAR-actively exposed and 83 non-OAR- actively exposed) willing and apparently healthy male and female adult subjects. Following receipt of ethical approval and consent, five milliliter of blood was taken from each subject from their antecubital vein after sterilizing the portion of the cubital fossa. The sample was then put into plain sample bottle and centrifuged to recover serum. Thereafter, the automated blood gas analyzer was used to measure the arterial blood gases of the subjects. The result showed marked (P<0.05) reductions in the partial pressure of oxygen (PO2) and oxygen saturation (SO2) levels in artisanal refinery operators (actively exposed) when compared to that of the passively-exposed subjects. Again, there were marked (P<0.05) elevations in the plasma pH and bicarbonate ions (HCO-3) levels in the actively exposed subjects compared to their passively-exposed counterparts. In conclusion, there could be adverse impact on respiratory blood gases and incidences of metabolic alkalosis over chronic exposures to the OAR activities.