A key step for the survival of the malaria parasite is the release from and subsequent invasion of erythrocytes by the merozoite. Differences in the efficiency of these two linked processes have a direct impact on overall parasite burden in the host and thereby virulence. A number of parasite proteases have recently been shown to play important roles during both merozoite egress as well as merozoite invasion. The rodent malaria parasite Plasmodium yoelii has been extensively used to investigate the mechanisms of parasite virulence in vivo and a number of important proteins have been identified as being key contributors to pathology. Here we have utilized transcriptional comparisons to identify two protease-like SERAs as playing a potential role in virulence. We show that both SERAs are non-essential for blood stage development of the parasite though they provide a subtle but important growth advantage in vivo. In particular SERA2 appears to be an important factor in enabling the parasite to fully utilize the whole age repertoire of circulating erythrocytes. This work for the first time demonstrates the subtle contributions different protease-like SERAs make to provide the parasite with a maximal capacity to successfully maintain an infection in the host.