Patients with idiopathic pulmonary fibrosis (IPF) often do worse following infection, but the cause of the decline is not fully understood. We previously demonstrated that infection with a murine gamma herpes virus (HV-68) could exacerbate established lung fibrosis following administration of fluorescein isothiocyanate. In this study, we anesthetized mice and injected saline or bleomycin intratracheally on day 0. On day 14, mice were anesthetized again and infected with either a Gram negative bacteria (Pseudomonas aeruginosa), or with H1N1 or HV-68 viruses. Measurements were then made on days 15, 21 or 35. We demonstrate that infection with P. aeruginosa does not exacerbate extracellular matrix deposition post-bleomycin. Furthermore, fibrotic mice are effectively able to clear P. aeruginosa infection. In contrast, bleomycin-treated mice develop worse lung fibrosis when infected with HV-68, but not when infected with H1N1. The differential ability of HV-68 to cause increased collagen deposition could not be explained by differences in inflammatory cell recruitment or whole lung chemokine and cytokine responses. Alveolar epithelial cells from HV-68-infected mice displayed increased expression of TGFβ receptor 1, increased SMAD3 phosphorylation and evidence of apoptosis measured by cleaved poly ADP ribose polymerase (PARP). The ability of HV-68 to augment fibrosis required the ability of the virus to reactivate from latency. This property appears unique to HV-68, as the β herpes virus, cytomegalovirus, did not have the same effect.