Influenza infection of humans remains an important public health problem. Vaccine strategies result in a significant but only partial control (65–85%) of infection. Thus, chemotherapeutic approaches are needed to provide a solution both for vaccine failures and to limit infection in the unvaccinated population. Previously (Walsh et al., 2011, Teijaro et al., 2011) documented that sphingosine-1-phosphate 1 receptor (S1P1R) agonists significantly protected mice against pathogenic H1N1 influenza virus by limiting immunopathologic damage while allowing host control of the infection. Here we extend that observation by documenting S1P1R agonist can control pathogenic H1N1 influenza infection in ferrets. S1P1R agonist was more effective in reducing pulmonary injury than the antiviral drug oseltamivir but, importantly, combined therapy was significantly more effective than either therapy alone.