Post-exposure prophylaxis (PEP) for potential lyssavirus exposures consists of wound management, rabies vaccination and may include rabies immunoglobulin (RIG). Rabies serology is sometimes indicated if there is risk of PEP failure. ObjectivesEvaluate the benefit of serology by indication. MethodsChart review of potential lyssavirus exposures managed at a Public Health Unit (June 2015 – December 2022) where serology was requested was conducted. The proportion of non-therapeutic titres was compared by sex, age, Indigenous status, serology indication, and whether RIG was given. Results46 notifications with serology were included. Males (5/19) and people over 40 (3/16) were more likely to demonstrate a non-therapeutic response. 2/3 of cases where vaccine doses were not given in the deltoid were non-therapeutic. The rate of non-therapeutic titres was similar for RIG given into the ipsilateral arm (2/11) and given excess RIG for weight (1/4). Although this small sample was inconclusive in isolation, it was also noted that all cases who did not receive RIG had therapeutic serology, whereas 6/35 of those receiving RIG had non-therapeutic serology. ConclusionsThis study supports broader literature questioning the utility of systemic RIG administration as likely limited and potentially detrimental considering the increased risk of immune interference. Implications for public healthHighlights a need to review Australian national guidelines to align with World Health Organization advice recommending local RIG administration only.