BACKGROUND: Surgical site infection (SSI) is a common postoperative concern. PURPOSE: To provide an in-depth understanding of the lived experience and quality of life (QoL) of individuals with SSI. METHODS: A systematic search for published studies that explored the impact of SSI on QoL among adult patients (older than 18 years) who had undergone any type of surgery was performed in June 2020. The search included but was not limited to MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane databases using the terms “surgical site infection” OR “hospital-acquired infection” OR “nosocomial infection” OR “wound site infection” OR “surgical wound site infection” AND “Quality of Life” OR “Life quality” OR “Health-Related Quality of Life” OR “Life Style” OR “QOL” OR “HRQoL” OR “Short-form questionnaire 36” OR “Questionnaire SF-36” OR “SF-36.” All quantitative and qualitative study designs were included; no language or date of publication restrictions were imposed. The Critical Appraisal Skills Program Qualitative Checklist was used to assess the methodological quality of the included studies. Study author, date, setting, sample size, population, and design and type of surgery as well as QoL instrument scores were extracted. A narrative thematic synthesis, which comprised the physical, psychological, social, economic, and spiritual effects as well as the health care worker–patient relationship, was undertaken for qualitative studies. Outcome measures were collected and assessed using a range of established health QoL instruments and reported in terms of QoL for quantitative studies. In addition, the type of QoL instrument employed within the studies was elucidated for comparing the scores of the instruments. RESULTS: A total of 696 publications were found; 690 were eliminated, leaving 4 quantitative and 2 qualitative studies conducted between 2002 and 2018 that met the inclusion criteria. The total number of participants in the assessed studies was 785. The mean sample size for the included studies was 131 participants (SD = 192.5; median, 95). Thematic synthesis showed 6 overarching themes: physical, psychological, social, spiritual, and economic effects of SSI as well as the health care worker–patient relationship. Short Form-36 was used to assess QoL in 3 of the 4 quantitative studies; these studies showed that there were decrements in scores of Short Form-36. CONCLUSION: Although this systematic review included heterogeneous groups of patients who underwent different surgical procedures and completed different QoL assessment tools, patients with SSI experienced low QoL, with limitations in physical, social, and psychological functioning. The health care worker–patient relationship was predominantly perceived negatively. Further prospective research is warranted.