Viral Nervous Necrosis (VNN, also called viral encephalo- and retinopathy (VER)), is a widespread disease of marine aquaculture caused by betanodavirus (or nervous necrosis virus - NNV), a segmented positive sense RNA virus, member of the nodaviridae family. VNN affects predominantly marine fish and cause significant losses to the Mediterranean fish farming industry, including the production of European sea bass (Dicentrarchus labrax). Of the four circulating genotypes of betanodavirus, red-spotted grouper NNV (RGNNV) and the reassortant genotype red-spotted grouper/striped jack NNV (RG/SJNNV) are most prevalent in the Mediterranean. Inheritable resistance against VNN has been detected in sea bass, and selective breeding could be a mean to limit this untreatable disease. In the current study, we compare resistance to disease among three populations from the Atlantic Ocean (AT), Eastern Mediterranean (EM) and Western Mediterranean (WM), by challenge trials using both a highly pathogenic isolate of RGNNV and a lower pathogenic reassortant isolate of RG/SJNNV. The survival of the three populations were modelled with a logistic regression, and the odds ratio (OR) of surviving was calculated. The challenge with RG/SJNNV reduced the odds of surviving three-fold (OR = 0.29 [0.07-0.87]), whereas the challenge with RGNNV reduced the odds of surviving 100-fold (OR = 0.01 [0.00-0.03]). Overall, the EM population had 3.32 (1.92–5.86) times higher odds of surviving the challenge than the AT and WM stocks. All survivors were harboring viral RNA in the brain, as demonstrated by RT-qPCR. However, viral RNA levels were in average lower in survivors from the EM population in both challenges, though only significantly lower in the challenge with RG/SJNNV (p < 0.01). The survival results combined with the RT-qPCR results indicate that the EM sea bass population has a natural resistance to disease caused by RGNNV, possibly associated with limited viral entry into and/or replication in the brain.