The current investigation evaluated the alleviating effects of vitamin C and vitamin E on oxidative stress, hematobiochemical, and histopathological changes in the kidney induced by copper sulfate (CuSO4) toxicity in chickens. Two hundred and fifty-one-day-old male broiler chicks were randomly allotted into five experimental groups (five replicates/group, ten chicks/replicate): 1st group—basal diet with no additives (control group), 2nd group—basal diet complemented with CuSO4 (300 mg/kg diet), 3rd group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet), 4th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin E (250 mg/kg diet), and 5th group—basal diet with CuSO4 (300 mg/kg diet) + vitamin C (250 mg/kg diet) + vitamin E (250 mg/kg diet) for a 42 day feeding period. The results showed a significant reduction in red blood cells (RBCs), hemoglobin (Hb) concentration, and hematocrit values as well as total leukocyte counts (WBCs), lymphocyte, heterophil, and monocyte counts in the CuSO4-intoxicated birds (2.42 × 106/µL, 9.54 g/dL, 26.02%, 15.80 × 103/µL, 7.86 × 103/µL, 5.26 × 103/µL, and 1.18 × 103/µL, respectively, at the 6th week) compared to (2.79 × 106/µL, 10.98 g/dL, 28.46%, 21.07 × 103/µL, 10.84 × 103/µL, 7.12 × 103/µL, and 1.60 × 103/µL, respectively) in the control group. Moreover, CuSO4-intoxicated birds showed hypoglycemia with a rise in serum uric acid and creatinine levels (122.68, 5.18, and 0.78 mg/dL at the 6th week) compared to (159.46, 4.41, and 0.61 mg/dL) in the control group. The CuSO4 toxicity in birds induced oxidative stress, indicated by a high serum malondialdehyde level (MDA) and diminished activity of the antioxidant enzymes (glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD)) (2.01 nmol/mL, 37.66 U/mL, and 2.91 U/mL, respectively, at the 6th week) compared to (1.34 nmol/mL, 57.00 U/mL, 4.99 U/mL, respectively) in the control group. High doses of Cu exposure caused severe microscopic alterations in kidney architecture. The addition of vitamins C and E, singularly or in combination, displayed a beneficial effect in alleviating these harmful effects of Cu toxicity. These findings showed the possible mitigating impacts of dietary antioxidants on the hematobiochemical alterations, oxidative stress, and kidney damage induced by CuSO4 toxicity.