Background Influenza is a persistent public health problem with a significant burden on patients, employers, and society. A systematic review by Keech and Beardsworth (2008) characterized the burden of influenza/influenza-like illness (ILI) on absenteeism. We conducted a systematic literature review evaluating the impact of influenza/ILI on work productivity among adults as an update to the work of Keech and Beardsworth. Methods This systematic review identified studies evaluating the impact of influenza/ILI on absenteeism, presenteeism, or related work productivity measures for employees and employed caregivers based on laboratory confirmation, physician diagnosis, and/or self-reported illness. Eligible studies were in English, French, or German published from 7 March 2007 through 15 February 2022, in PubMed, Embase, or BIOSIS. Two reviewers completed screening and full-text review, with conflicts resolved by a third advisor. Summary data were extracted by two analysts; all records were quality checked by one analyst. Work productivity outcomes were summarized qualitatively, and risk of bias was not evaluated. Results A total of 14,387 records were retrieved; 12,245 titles/abstracts were screened and 145 full-text publications were reviewed, of which 63 were included in the qualitative assessment. Studies of self-reported ILI were most frequent (49%), followed by laboratory-confirmed cases (37%) and physician diagnoses (11%). Overall, approximately 20–75% of employees missed work due to illness across study settings and populations. Mean time out of work among ill employees varied widely across study designs and populations, ranging from < 1 to > 10 days, and was often reported to be approximately 2–3 days. Considerable heterogeneity was observed across study designs, populations, and outcomes. Most employees (≈ 60–80%) reported working while experiencing influenza/ILI symptoms. Reporting of costs was sparse and heterogeneous; one study reported annual costs of influenza-related absences equating to $42,851 per 100,000 employee health plan members. Results were partitioned based on the following categories. Among otherwise healthy adults, 1–74% of workers missed ≥1 workday due to influenza/ILI, for a mean [standard deviation (SD)] of 0.5 (1.44) to 5.3 (4.50) days, and 42–89% reported working while ill, for a mean (SD) of 0.3 (0.63) to 4.4 (3.73) days. Among working caregivers, 50–75% missed work to care for children/household members with influenza/ILI, for 1–2 days on average. Similarly, the mean absenteeism among healthcare workers ranged from 0.5 to 3.2 days. Across studies evaluating vaccination status, generally smaller proportions of vaccinated employees missed time from work due to influenza/ILI. Conclusions This systematic review summarized the productivity burden of influenza/ILI on the worldwide working-age population. Despite notable heterogeneity in study designs, influenza/ILI case definitions, a...