White spot syndrome virus (WSSV) infects several economically important aquaculture species, and has caused significant losses to the industry. This virus belongs to the Nimaviridae family and has a dsDNA genome ranging between 257 and 309 kb (more than 20 isolate genomes have been fully sequenced and published to date). Multiple routes of infection could be the cause of the high virulence and mortality rates detected in shrimp species. Particularly in Penaeus vannamei, differences in isolate virulence have been observed, along with controversy over whether deletions or insertions are associated with virulence gain or loss. The pathogenicity of 3 isolates from 3 localities in Mexico (2 from Sinaloa: ‘CIAD’ and ‘Angostura’; and one from Sonora: ‘Sonora’) was evaluated in vivo in whiteleg shrimp P. vannamei infection assays. Differences were observed in shrimp mortality rates among the 3 isolates, of which Sonora was the most virulent. Subsequently, the complete genomes of the Sonora and Angostura isolates were sequenced in depth from infected shrimp tissues and assembled in reference to the genome of isolate strain CN01 (KT995472), comprising 289350 and 288995 bp, respectively. Three deletion zones were identified compared to CN01, comprising 15 genes, including 3 envelope proteins (VP41A, VP52A and VP41B), 1 non-structural protein (ICP35) and 11 other encoding proteins whose function is currently unknown. In addition, 5 genes (wsv129, wsv178, wsv204, wsv249 and wsv497) presented differences in their repetitive motifs, which could potentially be involved in the regulation of gene expression, causing virulence variations.