Acute toxicity experiments were conducted to determine the lethal concentration 50 (LC50) of the Up Grade®46% SL for Oreochromis niloticus. Our results showed that the 96-h LC50 value of UPGR for O. niloticus was 29.16 mg L-1. To study hemato-biochemical effects, fish were exposed for 15 days to individual UPGR at 2.916 mg L-1, individual polyethylene microplastics (PE-MPs) at 10 mg L-1, and to their combinations UPGR+PE-MPs. UPGR exposure induced significant decrease in account of red blood cells (RBCs) and white blood cells (WBCs), platelets, monocytes, neutrophils, eosinophils, and the concentrations of hemoglobin (Hb), hematocrit (Hct), and mean corpuscular hemoglobin concentration (MCHC) than other treatments, compared to the control group. Sub-acute UPGR exposure significantly increase lymphocytes, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), compared to the control group. In conclusion, UPGR and PE-MPs displayed antagonistic toxic effects due to maybe the sorption of UPGR onto PE-MPs.