Environmental variation has important effects on host-pathogen interactions, affecting large-scale ecological processes such as the severity and frequency of epidemics. However, less is known about how the environment modulates viral fitness traits and within host infection processes. Viral genetic variation, fish host immune response and environmental parameters such as temperature have been reported to strongly influence the replication and clearance of infectious hematopoietic necrosis virus (IHNV), a significant pathogen of salmon and trout. Here, we quantified the effect of water temperature on probability of infection across time following exposure of steelhead (Oncorhynchus mykiss) to a field isolate of IHNV. Warm water temperatures accelerated IHNV replication compared to colder water temperatures in cell lines, which have a more limited host immune response. In vivo challenge experiments also demonstrated a higher replication rate of IHNV at warmer water temperatures, but IHNV persisted for a shorter amount of time at these warmer temperatures and led to lower overall mortality compared to colder temperatures. Furthermore, fish were found to have higher prevalence of neutralizing antibodies at warmer water temperatures compared to colder temperatures. These results support the hypothesis that IHNV clearance or persistence is modulated by temperature, and this difference was influenced by temperature effects on the host immune responses. At later time points, the viral RNA that persisted was most commonly localized in the kidney and spleen pooled tissue; these tissues are composed of hematopoietic cells that are favored targets of the virus. By partitioning the effect of environmental variation into independent and common effects of host and pathogen responses, we can better understand the environmental regulation of host-pathogen interactions within hosts. Our results therefore provide insights into how different host-pathogen systems could react to environmental change.