Frailty is a multidimensional syndrome of reduced physiological reserve and heightened vulnerability to stressors. Frailty is common among older adults and linked to adverse outcomes including disability, hospitalisation and death. Infections are common in older populations and remain a major cause of morbidity and death. Although it has been suggested that infections influence frailty development and progression (via inflammatory and functional mechanisms), evidence from longitudinal studies is inconsistent. Therefore, we aim to assess longitudinal associations between infections and frailty in adults.

We will conduct a systematic review of observational cohort and case-control studies examining associations between infections and frailty in adults. We will search MEDLINE, Embase and Global Health from 2001 to February 2026 without language restrictions. Two reviewers will independently screen titles and abstracts and subsequently assess full texts for eligibility. Data will be extracted using a standardised data extraction form. Risk of bias will be assessed using a customised domain-based tool based on the Risk Of Bias In Non-randomised Studies of Exposures (ROBINS-E) framework. We will initially narratively synthesise our findings. Where studies are sufficiently homogeneous, we will undertake random effects meta-analysis. We will assess the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Ethical approval is not required for a systematic review. Results of the review will be published in a peer-reviewed journal and disseminated through conferences.

CRD420261299590.