The effects of the lipopolysaccharide (LPS) from Ochrobactrum intermedium was evaluated in sheep experimentally infected with Fasciola hepatica. Animals were divided into four groups: two treated with the LPS (T1/T2) and two controls (C1/C2). T1/C1 were slaughtered at 30 days postinfection (dpi) and T2/C2 at 85 dpi. Body weight and body condition were found higher in T1 and T2 than in controls, although differences were not significant. Treated sheep showed lower cumulative fecal egg count than controls (p < 0.01). Levels of red blood cells (RBC), white blood cells, hemoglobin, and hematocrit (HCT) were higher in T1 and T2. Significant differences (p < 0.05) in RBC and HCT were found between groups at 84 dpi. More severe macrocytic and hypochromic anemia was observed in C1 and C2 than in treated groups. Total protein and albumin values were higher in T1 and T2 (p < 0.01) until 29 dpi. At the end of the trial, no significant differences were observed in hepatic enzymes, although gamma-glutamyl transferase and aspartate aminotransferase values were higher in C2, and alanine aminotransferase was higher in T2. At necropsy, the mean weight of liver, fibrosis in portal triads, and ganglion size were similar in all groups. The number and size of flukes was greater in C2 than in T2 (p < 0.05). The histological examinations revealed a higher degree of parenchymatous fibrosis in T2 compared to C2 (p < 0.05). The administration of LPS from O. intermedium increased the nonspecific resistance against F. hepatica in experimentally infected sheep.