Background: Depression and anxiety can significantly impact workplace productivity, for instance, by increasing absenteeism and presenteeism. This loss of productivity leads to diminished workplace economic outcomes. Internet-based cognitive behavioral therapy (iCBT) has emerged as a cost-effective intervention within workplace settings that improves workplace productivity loss due to depression and anxiety, but more generalizable evidence beyond the workplace, such as in a national health service setting, is lacking. Objective: This naturalistic, repeated-measures, retrospective study investigated the impact of iCBT on work productivity metrics using nationally representative data from patients enrolled in the Irish national health service (ie, the Health Service Executive). Methods: We analyzed repeated measures retrospective data from 7125 employed patients enrolled in iCBT at the Health Service Executive between March 2023 and May 2024. The Work Productivity and Activity Impairment questionnaire was used to measure absenteeism, presenteeism, overall productivity loss, and activity impairment. Secondary outcomes included depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7). Patients were primarily 25 to 64 years old (n=5578, 78%), female (n=4956, 70%), and met clinical scoring criteria on the Patient Health Questionnaire-9 or Generalized Anxiety Disorder-7 (n=4774, 67%). Missing data were handled using multiple imputation. We used mixed-effects models to assess pre-post treatment changes in outcomes and then utilized Irish national salary estimates from 2022 to derive cost savings (in 2022 € values; €1=approximately US $1.05) based on productivity improvement during use of the iCBT program. Results: From baseline to follow-up, absenteeism reduced by 6.85% (