ABSTRACTUnderstanding the pathogenicity of viral infections in aquatic organisms is vital due to their substantial impact on aquaculture and wild populations. This study assessed the pathogenicity of Callinectes sapidus Reovirus 2 in Callinectes danae and its effects on the metabolic, immunological and behavioural parameters. CsRV2‐negative specimens were divided into CsRV2 inoculum (n = 10) and saline injection (n = 15). After 14 days, all the crabs that received the inoculum tested positive for CsRV2. However, 11 crabs from the control group also tested positive and were subsequently considered an additional experimental group. The cumulative mortality in the group challenged reached 70% after 14 days. RT–PCR revealed Callinectes danae Portunibunyavirus 1 presence in CsRV2‐injected crabs, explaining heightened mortality. Ammonia flow remained unaffected, but oxygen consumption was significantly impacted (p < 0.05) by CsRV2 and coinfection, suggesting increased metabolic energy expenditure. The coinfection caused an increase in the proportion of crabs with reflex impairment as a likely consequence of physiological exhaustion. Additionally, there was a trend toward reducing the number of granulocytes in coinfected crabs, indicating that granulocytes may be more affected by coinfection. These findings demonstrate the pathogenicity of CsRV2 in C. danae, with coinfection exacerbating metabolic, behavioural and immunological changes, increasing mortality.