PURPOSE: We performed a systematic review with meta-analysis examining the relationship between pain or pain medications and delirium occurence, duration, and severity. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials from inception to May 15, 2023. We included randomised or observational studies among critically ill adults, that reported data on pain or exposure to analgesics, and reported delirium presence, duration, or severity with no language or region restrictions. PROSPERO ID: CRD42022367715. Two authors independently screened records and extracted data. Risk of bias was evaluated using Risk of Bias 2 or the Risk of Bias In Non-randomized Studies of Interventions. We pooled data using the Hartung-Knapp Sidik-Jonkmann random effects model. PRISMA was followed. RESULTS: From 8,054 citations, 90 studies (119,230 patients) published between 2001 and 2023 were included in the systematic review. 41 studies were included in the primary meta-analysis examining prevalent delirium: seven studies evaluated pain; 12 studies evaluated fentanyl; and five studies evaluated morphine. There was a trend to association between pain and delirium occurrence (OR 2.49, 95% CI 0.98-6.30), and a significant association between pain and incident delirium (OR 3.70, 95% CI 1.73-7.93). Fentanyl (OR 2.49, 95% CI 1.45-4.27) and morphine (OR 2.13, 95% CI 1.21-3.75) were associated with delirium occurrence. Risk of bias was critical for many studies. CONCLUSIONS: We observed an association between pain and incident delirium among critically ill adults. Exposure to morphine or fentanyl (but no other pain medications) was associated with increased risk of delirium occurrence.