Much research has concentrated on the seed extracts of Piper guineense and not on the leaves which are widely consumed and hence this study. Fifteen male wistar rats weighing 150-250g were randomly divided into control, low dose (LD) and high dose (HD) groups of five rats each. LD and HD groups received 250mg/kg and 350mg/kg b.w. respectively of aqueous leaf extract of Piper guineense by gavaging. Duration of feeding was thirty days. The results showed significant increases (p<0.001) in serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in both LD and HD groups compared with control. Serum total cholesterol (TC) was significantly (p<0.001) increased in both LD and HD groups compared with control. Serum triglyceride (TG) was significantly increased in HD group compared with control (P < 0.001) and LD (P<0.001) groups. High density lipoprotein (HDL-c) was significantly increased (p<0.001) in LD compared with control and decreased (p<0.001) in HD compared with control and LD groups. Low density lipoprotein (LDL-c) was significantly increased in LD (p<0.001) and HD (p<0.01) compared with control and decreased in HD (p<0.001) compared with LD. TG/HDL-c in the HD group was significantly (p<0.001) increased compared with control and LD groups. Aside RBC count and MCH which were significantly increased (p<0.05) and decreased (p<0.05) respectively in HD compared with LD group, all other haematological parameters (Hb, PCV, MCHC, MCV and WBC and platelet counts) did not differ significantly among the groups. In conclusion, consumption of aqueous leaf extract of Piper guineense causes dyslipidemia and elevation of liver enzymes but no significant effect on hematological indices.