Recent studies have shown that transportation networks are important in the dissemination of the influenza virus. Moreover, epidemiological models that are used to predict the spatial dynamics of an influenza epidemic have been found to be more accurate when incorporating human mobility data. Yet, the majority of the studies that have explored the association between transportation networks and influenza have done so at a global or regional scale, with very little conducted at finer scales. As such, the objective of this paper is to explore the link between transit, influenza, and weather data at a city-level scale and to compare results between three cities and one county: Boston, Chicago, Washington DC, and Franklin County, OH. Findings show that there is a consistent negative correlation between influenza indicators and public transportation ridership across all locations. Such correlations are not consistent with the findings of studies performed at more “macroscopic” scales where transportation usage is not necessarily associated with public transit usage and where inclement weather conditions do not play a significant role in the usage of a given transportation mode. According to the findings, the authors propose the following hypothesis: weather conditions could help determine the demand for public transit and, therefore, the risk of exposure of an individual to other infected riders on public transportation as the flu season progresses and weather conditions change. This suggests a correlation between weather conditions, public transit usage, and influenza contagion and should therefore be considered jointly when designing public health interventions. Additionally, flu infection of riders may influence public transit demand during the flu season. However, more research is needed to corroborate this hypothesis.