Owing to their abundance and diversity, it is generally perceived that viruses are important for structuring microbial communities and regulating biogeochemical cycles. The ecological impact of viruses on microbial food webs, however, may be influenced by evolutionary processes, including the ability of bacteria to evolve resistance to viruses and the theoretical prediction that this resistance should be accompanied by a fitness cost. We conducted experiments using phylogenetically distinct strains of marine Synechococcus (Cyanobacteria) to test for a cost of resistance (COR) to viral isolates collected from Mount Hope Bay, Rhode Island. In addition, we examined whether fitness costs (1) increased proportionally with 'total resistance', the number of viruses for which a strain had evolved resistance, or (2) were determined more by 'compositional resistance', the identity of the viruses to which it evolved resistance. A COR was only found in half of our experiments, which may be attributed to compensatory mutations or the inability to detect a small COR. When detected, the COR resulted in a approximately 20% reduction in relative fitness compared to ancestral strains. The COR was unaffected by total resistance, suggesting a pleiotropic fitness response. Under competitive conditions, however, the COR was dependent on compositional resistance, suggesting that fitness costs were associated with the identity of a few particular viruses. Our study provides the first evidence for a COR in marine bacteria, and suggests that Synechococcus production may be influenced by the composition of co-occurring viruses.