Influenza increases the risk of secondary diseases, but other than pneumonia, many of these diseases (e.g., sinusitis, otitis media, acute myocardial infarctions) are not consistently considered in estimates of influenza burden. We used the Merative Marketscan database (2001–2019) and time-series methods to identify age-specific categories of diseases that were temporally associated with patterns of influenza activity. Next, we estimated hypothetical reductions in the incidence and costs of these diseases if influenza incidence were reduced. Of 282 different disease categories evaluated, 23 (8.2%) were strongly associated with influenza (e.g., acute bronchitis, otitis media, myocardial infarctions, sinusitis, COPD) in at least one age group. For example, we estimated a 20% decrease in peak influenza incidence could decrease acute bronchitis cases by 6.5% and pneumonia cases by 5.3%, corresponding to a $1.6 billion reduction in healthcare costs. Excluding secondary diseases associated with influenza may lead to substantial underestimates of influenza’s burden and costs.