Despite vaccine efforts, influenza outbreaks pose a significant threat to global public health. There are two commercially available seasonal influenza vaccines in the United States: the trivalent inactivated vaccine (TIV), delivered parenterally, and the live attenuated influenza vaccine (LAIV), delivered intranasally. Although both vaccines are generally efficacious, the immunologic mechanisms which contribute to protective immunity are incompletely understood. Thus, we investigated the protracted effects of TIV and LAIV on serum cytokine profiles at 14 and 28 days post-vaccination (when antibody titers are peak) in healthy adults over two influenza seasons. Vaccination with TIV was associated with a small, yet significant, decrease in the levels of both IL-8 and TNF-α at 14 and 28 days post-vaccination. LAIV, however, had no impact on serum cytokine levels. Similarly, analysis of serum antibody titers indicated that TIV recipients had a significantly higher sero-response rate compared to LAIV recipients, as has been previously shown. Finally, we examined the relationship between baseline serum cytokine levels and antibody responses to TIV (LAIV recipients were excluded due to the poor sero-response rate). Interestingly, in TIV recipients pre-vaccination levels of IL-8 were higher in sero-responders compared to non-responders. Collectively, these data suggest that cytokines may influence vaccine outcomes and indicate that parenteral immunization with TIV induces a sustained, systemic cytokine response which lasts for weeks.