BACKGROUND: In terminally ill cancer patients approaching the dying phase, liberal use of antimicrobials is often viewed by palliative care experts as irrational. No previous reports have reviewed current antimicrobial use in palliative care settings in Saudi Arabia. OBJECTIVE: The objective of this study was to explore the pattern of antimicrobial use in a tertiary palliative care unit (TPCU) during the last week of patients’ life. METHODS: Medical records of all patients who died in the TPCU over a 14-month period were reviewed for demographics as well as the frequency and rationale of antimicrobial use during the patients’ last week of life. Information on antimicrobial use was obtained from a computerized pharmacy database. RESULTS: Of 138 patients who died with advanced cancer in the TPCU, 87 (63%) were on one or more antimicrobials during their last week of life. Antibiotics were more frequently used as compared to antifungal and antiviral agents, 64 (46.4%); 45 (32.6%); and 2 (1.5%), respectively. About one third (31.3%) of patients who received antibiotics during their last week of life were prescribed more than one antibiotic. Antimicrobials were mostly given systemically (79%) rather than topically (21%). The most common rationales for antimicrobial prescribing were oral thrush in 36 patients (25.4%), wound care in 29 patients (20.4%), and on empirical basis in 29 patients (20.4%). CONCLUSIONS: The current practice of antimicrobial prescribing, especially for patients who are eminently dying, may need to be reviewed. Initiation of antimicrobial treatment in this group of patients should be based on clear treatment goals and desired outcomes, considering views of patients and families.