Experiments were conducted to study the effect of using dried orange pulp (DOP), as an alternative energy source in the ration of Holstein dairy cows, on nutrient digestibility, blood constituents, level of antioxidants in plasma, and presence and count of fecal pathogenic bacteria e.g. E. coli and Salmonella spp. Forty lactating Holstein cows, weighing 550±50 kg, with an average of 20 kg daily milk yield, were randomly divided into four groups (ten in each group). Animals were fed rations containing DOP at 0, 25, 50 and 75% substitution of yellow corn grains (R1, R2, R3 and R4, respectively). Digestion trail was conducted in the last week of the experiment using Acid Insoluble Ash method. Feces samples were taken and analyzed in the same day for Salmonella spp. and E. coli and blood samples for analysis were taken from the subcutaneous abdominal vein. The experimental rations were almost identical in chemical composition. Results of nutrient digestibility and nutritive value, as total digestible nutrients (TDN) and digestible crude protein, showed that there were insignificant (P>0.05) differences between cows fed R2, R3 and R4 compared with those fed R1 (control), except digestibility of nitrogen free extract which was significantly (P≤0.05) decreased by feeding experimental rations by increasing replacement level of DOP to more than 25% (R2). Blood constituents of experimental cows on all rations were within normal range for platelets, red blood cells (RBCs), hematocrit, hemoglobin (Hb, g/dl), alanine transaminase (ALT), aspartate transaminase (AST), total protein (g/dl), albumin (g/dl), creatinine (mg/dl) and urea. However, white blood cells (WBCs), globulin and total lipids were significantly (P≤0.05) decreased by increasing the replacement level of DOP. Total lipids values decreased by increasing the replacement levels of DOP more than 25% (R2) and total antioxidant capacity (TAC) in blood plasma, regarded as a biomarker of oxidative stress in cows, was insignificantly (P>0.05) affected by feeding experimental rations and ranged from 0.420 to 0.433 mm/l. Salmonella spp. was not detected and E. coli was insignificantly (P>0.05) affected by feeding DOP rations. It could be concluded that DOP can be used as an alternative source of energy in Holstein dairy cow’s rations, replacing up to 75% of yellow corn grains without negatively effecting nutrient digestibility, nutritive values, as TDN or digestible CP, and without showing any harmful effect on animal health. More studies are needed to examine the effect of citrus by-products on presence of fecal E. coli and Salmonella species, and on antioxidant biomarkers.