In nature, plants are simultaneously challenged by biotic and abiotic stresses. However, little is known about the effects of these combined stresses for most crops. This work aimed to evaluate the responsed of the virus-resistant cowpea genotype BRS-Marataoã to the exposure of salt stress combined with CPSMV infection. Cowpea plants were exposed to 200 mM NaCl either simultaneously (SV plant group) or 24 h prior to the CPSMV infection [S(24 h)V plant group]. Physiological, biochemical, and proteomic analyses at 2 and 6 days post salt stress (DPS) revealed that cowpea significantly reprogrammed its cellular metabolism. Indeed, plant size, photosynthetic parameters (net photosynthesis, transpiration rate, stomatal conductance, and internal CO ₂ partial pressure) and chlorophyll and carotenoid contents were reduced in S(24 h)V compared to SV. Moreover, accumulation of viral particles at 6 DPS in S(24 h)V was observed indicating that the salt stress imposed prior to virus infection favors viral particle proliferation. Proteomic analysis showed differential contents of 403 and 330 proteins at 2 DPS and 6 DPS, respectively, out of 733 differentially abundant proteins between the two plant groups. The altered leaf proteins are involved in energy and metabolism, photosynthesis, stress response, and oxidative burst. Biological significance: This is an original study in which a virus-resistant cowpea genotype (BRS-Marataoã) was (i) exposed simultaneously to 200 mM NaCl and inoculation with CPSMV (SV plant group) or (ii) exposed to 200 mM NaCl stress 24 h prior to inoculation with CPSMV [S(24 h)V plant group]. The purpose was to shed light on how this CPSMV resistant cowpea responded to the combined stresses. Numerous key proteins and associated pathways were altered in the cowpea plants challenged with both stresses, but unexpectedly, the salt stress imposed 24 h prior to CPSMV inoculation allowed viral proliferation, turning the cowpea genotype from resistant to susceptible.