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Blood chemistry of growing male pigs fed low crude protein (CP) and low-energy diets supplemented with multi-enzyme was determined using 36 male pigs aged 8–10-weeks old. Two metabolizable energy (3000 and 2600 kcal ME /kg) and three protein (18, 16, and 14% CP) levels were used to formulate 6 treatment diets: T1 (3000 kcal ME/kg and 18% CP), T2 (3000 kcal ME/Kg and 16% CP), T3 (3000 kcal ME/kg and 14% CP), T4 (2600 kcal ME/kg and 18% CP), T5 (2600 kcal ME/kg and 16% CP) and T6 (2600 kcal ME/kg and 14% CP). T1 served as the control diet, while T2–T6 was supplemented with 1.0 g enzyme/kg feed each. The treatments were replicated thrice with two pigs per replicate in a 2 × 3 factorial and analysed statistically. Serum total protein, albumin, globulin, albumin/globulin ratio, urea, creatinine, urea/creatinine ratio, cholesterol, alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) were analysed. Low-energy diets (3000 and 2600 kcal ME/kg) plus enzyme supplementation did not affect (P > 0.05) any of the serum parameter measured. Also, dietary low CP level plus enzyme supplementation influenced (P < 0.05) aspects of the serum parameters. Higher (P < 0.05) total protein, albumin and creatinine were noticed in pigs fed with T2 diet; while pigs fed with T4 diet had higher (P < 0.05) urea compared with those on the other 5 treatment diets. Significant dietary interaction effects (P < 0.05) were observed on cholesterol, ALT, AST and ALP. The quadratic regression model revealed that aspects of serum parameters in pigs were optimized at different low-protein and low-energy levels. In conclusion, the results suggest that pigs on T2 diet had the best serum parameters.