The primary objective of this study was to assess trends in employer expenditures for both direct medical costs and indirect productivity losses associated with influenza. A retrospective analysis was performed using two of the MarketScan family of databases for 2005–2009. Patients with at least one diagnosis claim for influenza during an influenza season were selected. We estimated seasonal incidence of influenza in the employed population from the MarketScan Commercial Claims and Encounters database. Health care utilization and costs and productivity losses were assessed during the 21-d period following the influenza diagnosis date. Compared with the 2005–2006 season (493 per 100,000 plan members), influenza incidence increased during the 2006–2007 (598 per 100,000 plan members) and 2007–2008 (1,142 per 100,000 plan members) seasons and had a dramatic increase during the pandemic season of 2008–2009 (1,715 per 100,000 plan members) . The total influenza-related employer spending per 100,000 plan members also increased by over 400% during the 2008–2009 influenza season [$623,248; confidence interval (CI]):$601,518-$644,991], compared with 2005–2006 ($145,834; 95% CI: $135,067-$156,603). The primary drivers of the increased costs were emergency room, outpatient and inpatient visits. Total costs associated with influenza-related missed work time per 100,000 plan members increased over 4-fold from $26,479 in the 2005–2006 influenza season to $122,811 in 2008–2009. Overall, as expected, considerably higher direct and indirect costs were observed during the 2008–2009 influenza pandemic season than during other influenza seasons. In recent years, the influenza-related employer burden has increased considerably. In future, employers may need efficient resource allocation in order to address the productivity losses and increasing direct medical costs associated with increased influenza incidence. One of the strategies that employers may consider is increasing influenza vaccination rates among employees, which likely will help lower the influenza incidence and the associated downstream direct and indirect costs.