Experimental infections have been used to better comprehend the immune system of organisms, and to probe for additives that generate greater resistance and help reduce antibiotic use in aquaculture. We compared the immune response of juveniles of the Caribbean spiny lobster, Panulirus argus, infected naturally with Panulirus argus virus 1 (PaV1) versus organisms infected experimentally, to determine the analogy between both infectious processes. The immunological response was measured by hemagglutination activity, hemocyte count, and total phenoloxidase activity in plasma and hemocytes in 211 individuals that were either naturally infected (110), or had been injected with viral inoculum and followed for six months (101). The samples were classified into the following four groups according to the severity of the infection: 0, uninfected; 1, lightly; 2, moderately; and 3, severely infected), which was determined on the basis of PCR and histological criteria. A permutational MANOVA showed that both the origin (natural and experimental), and the severity of the infection contributed significantly to explain the variation in the immune response of lobsters. The lack of significance of the interaction term indicated that the immunological response changed with the severity of the infection in a similar way, regardless of its origin. The results of the present study suggest that the experimental viral infection of PaV1 produces a defense response similar to the natural pathways of contagion, and provides the bases to validate an immunological challenge protocol for the first time in crustaceans. The discussion includes the perspective of the conceptual models of immune response within an ecological context.