This paper uses a difference-in-differences (DID) framework to estimate the impact of Non-Pharmaceutical Interventions (NPIs) used to fight the 1918 influenza pandemic and control the resultant mortality in 43 U.S. cities. The results suggest that NPIs such as school closures and social distancing, as implemented in 1918, and when applied for a relatively long and sustained time, might have reduced individual and herd immunity and the population general health condition, thereby leading to a significantly higher number of deaths in subsequent years.