BACKGROUND: Yersiniosis is known as one of the most prevalent bacterial diseases in fish, which causes high mortality and economic losses in cultured fish farms every year. OBJECTIVES: The present study was conducted to investigate the changes in hematological indices and gut histopathology in Caspian roach (Rutilus caspicus) exposed to Yersinia ruckeri. METHODS: 60 Caspian roach broodstock with an average weight of 63.4 ± 2.1 g were divided into three groups (with two replicates for each group), including one treatment, one positive control, and one negative control groups. The treatment group was intraperitoneally injected with Yersinia ruckeri bacterium at a dosage of 3.8 × 107 cell/fish. The positive group just received normal saline (0.9 % NaCl) via intraperitoneal injection. No injection was performed in the negative control group. RESULTS: Symptoms appeared on the fourth day after exposure and 20 % of the fish in the treatment group died 5 days after the challenge. Cumulative mortality reached 53 % on day 9 after the challenge.  According to hematological analysis, the challenge with Yersinia ruckeri led to a significant increase in white blood cell counts (WBC) compared to the control groups. Moreover, 10 days following exposure, the treatment group experienced hypochromic macrocytic anemia. Gut histopathology was characterized with necrosis and detachment of intestinal epithelial cell and inflammatory cells infiltration in the treatment group. CONCLUSIONS: Based on the obtained results herein, Yersinia rackeri can cause acute disease in Caspian roach; therefore, preventing and controlling this disease is essential for these fish in infected regions.