BACKGROUND: Canine low-dose sepsis model provides a reliable setting to study innovative drugs. Li- popolysaccharides (LPS), a major constituent of bacterial outer membrane, have been demonstrated to play a critical role in the initiation of pathogenesis. Lipopolysaccharide-induced sepsis has been extensively studied in laboratory animals; but its importance has mainly remained unknown in dogs. OBJECTIVES: The aim of the present survey was to examine the effectiveness of quercetin, along with hydrocortisone on clinical and hematological alterations, and organ failure (liver and heart) in low-dose lipo- polysaccharide-induced canine sepsis model. METHODS: For this purpose, fifteen clinically healthy mixed dogs were randomly divided into three equal groups. Lipopolysaccharide (0.1 μg/kg, IV) was injected to dogs in group A (control). Group B was similar to group A, but quercetin bolus (2 mg/kg, IV, once) was injected 40 minutes after LPS injection. Group C was similar to group B; however, hydrocortisone bolus (2 mg/kg, IV, once) was administered instead of quercetin. Serum levels of glucose, total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine kinase isoenzyme muscle/brain (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin I (cTn-I) concentration were measured by commercial kits. RESULTS: In control group, red blood cells (RBCs), hemoglobin (Hb), and hematocrit (HCT) significant-  ly decreased and serum activities of AST, ALP, LDH, CK-MB, and plasma cTn-I significantly increased (P<0.05). RBCs, Hb, and HCT significantly increased in quercetin group, compared with hydrocortisone and control groups (P<0.05). Quercetin group significantly decreased LDH, CK-MB, and cTn-I compared with hydrocortisone and control groups (P<0.05). Quercetin significantly decreased AST in comparison to control group and ALP in comparison to hydrocortisone group, also (P<0.05). CONCLUSIONS: These results suggest that quercetin protects RBCs in the early stages of sepsis and de- creases organs dysfunction (heart and liver), therefore it has a positive influence on sepsis and may be more effective than routine corticosteroid (hydrocortisone) therapy.