This study aimed to investigate pathogenic microbial causes of mortalities in twenty rabbit flocks located in 4 governorates in Northwest of Delta Egypt during a period from 2019 to 2022.The mortality rate was varied from 10 to 90 % in either sex of different breeds and ages (15 day-18 month). Ten flocks (50%) were positive for Rabbit hemorrhagic disease virus (RHDV) by HA and RT-PCR. Phylogenetic analysis of the VP60 gene indicated one sample (MW455128) was classic RHDV and eight strains (MW455120 - MW455127) were variant RHDV2.Enteropathogenic Escherichia coli (EPEC) was the predominant isolated bacteria (60%), belonging to various serotypes (poly 1, O26 K60, poly 2, O55 K59, poly 2, O126 K71, poly 1, O111, and poly 3, O114), followed by K. pneumoniae (35%), which was determined to be virulent by PCR detection of the uge gene (80%) and rmpA (40%), while the kfu gene was absent. Staph. aureus and Pasteurella multocida represented (30%) for each, while pseudomonas aeruginosa (20%) and Salmonella was negative. Pathologically, apoptosis was the most prominent lesion observed in liver, kidney, intestine, spleen, lung and heart, also there were severe enteritis, abscess in lung, liver and kidney and suppurative bronchopneumonia. By immunohistochemistry the RHDV antigen was detected in hepatic, splenic, renal, pulmonary, and cardiac tissues. The findings of this investigation highpoints on the significance of RHDVs (classic G3-G5 and variant RHDV2 which become more predominant), EPEC, K. pneumonia, S. aureus, P. multocida and p. aeruginosa as rabbit pathogens causing mortalities in studied Egyptian provinces. So that, these results are important in any effort to control rabbit pathogens in Egypt