Copper is a micronutrient vital to several cellular energy metabolic processes and drives erythropoiesis. However, it affects cellular biological activities and causes oxidative damage when in excess. This study investigated the effects of copper toxicity on erythrocyte energy metabolism in male Wistar rats. Ten Wistar rats (150-170g) were randomly divided into 2 groups: control (given 0.1ml distilled water) and copper toxic (given 100mg/kg copper sulphate). Rats were orally treated for 30 days. Blood, collected retro-orbitally after sodium thiopentone anaesthesia (50mg/kg i.p.) into fluoride oxalate and EDTA bottles, was subjected to blood lactate assay and extraction of red blood cell respectively. Red blood cell nitric oxide (RBC NO), glutathione (RBC GSH), adenosine triphosphate (RBC ATP) levels, RBC hexokinase, glucose-6-phosphate (RBC G6P), glucose-6-phosphate dehydrogenase (RBC G6PDH), and lactate dehydrogenase (RBC LDH) activity was estimated spectrophotometrically. Values (Mean±SEM, n=5) were compared using Student’s unpaired T-test at p<0.05. Copper toxicity significantly increased RBC hexokinase (23.41±2.80µM), G6P (0.48±0.03µM), G6PDH (71.03±4.76nmol/min/ml) activities, ATP (624.70±57.36µmol/gHb) and GSH (3.08±0.37µM) level compared to control (15.28±1.37µM, 0.35±0.02µM, 54.41±3.01nmol/min/ml, 330.30±49.58 µmol/gHb, and 2.05±0.14µM respectively, p<0.05). Also, RBC LDH activity (145.00±19.88mU/ml), NO (3.45±0.25µM) and blood lactate (31.64±0.91mg/dl) level were lowered significantly compared to control (467.90±94.23mU/ml, 4.48±0.18µM and 36.12±1.06 mg/dl respectively, p<0.05). This study shows that copper toxicity increases erythrocyte glycolytic rate and glutathione production. This increase could be connected to a compensatory mechanism for cellular hypoxia and increased free radical generation.