Vibrio spp. are common pathogens infected Apostichopus japonicus, Crassostrea gigas and Atlantic salmon in the ocean, which leading to a variety of diseases. A representative bacterial strain NB-6 was isolated from the body wall of the moribund A. japonicus with skin ulceration syndrome. The strain was identified as rod-shaped bacteria and morphologically homogeneous through transmission electron microscopy analyses. Based on the genome sequencing and phylogenetic tree analysis, NB-6 strain was identified as Vibrio nereis. The experimental infections were conducted by infection A. japonicus seedlings with the V. nereis NB-6 strain, and the results showed that the survival rates were 75?%, 66.7?%, 32.1?% and 20?% in A. japonicus seedlings after challenge V. nereis with 6.1?×?10⁴, 6.1?×?10⁵, 6.1?×?10⁶, and 6.1?×?10⁷?cfu/mL, respectively. The infected A. japonicus showed inflammatory cell infiltration, the destruction of the epidermis, and disorganized condensed inflammatory cells in body wall. Vibrio phage vB_VneM_NB-1 was isolated from A. japonicus breeding pond silt in Dalian, China. The phage vB_VneM_NB-1 exhibited large burst sizes 180 pfu/cell. The adhesion rate of V. nereis NB-6 to coelomocytes significantly decreased from 1?% to 0.04?% under the condition of phage infection. In the analysis of coelomocyte apoptosis of A. japonicus, we found that phage vB_VneM_NB-1 could significantly inhibit V. nereis induced coelomocyte apoptosis in A. japonicus. Herein, phage efficacy indicated its potential use as an antibacterial agent to control virulent V. nereis infection A. japonicus in aquaculture.