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Introduction : There are concerns that opioids may be associated with an increased risk of infection. This safety issue is alarming given the widespread use of opioids in pain management. Areas covered : In this review, we summarize the pharmacologic aspects of opioids related to the immune system and to the assumed pathophysiology of opioid-related infections. We also synthesize and critically appraise the available clinical evidence on the potential association between the use of opioids and the risk of infection. PubMed was searched from inception to 1 February 2019 for all articles published in English with terms corresponding to 'opioids' and 'infections'. Expert opinion : Morphine appears to suppress the immune system via affecting cells of the innate and the adaptive immunity as well as via modulating the hypothalamic-pituitary-adrenal axis. However, knowledge gaps exist regarding the immune-related pharmacology of non-morphine opioids. Observational studies have suggested an increased risk of infections associated with the use of opioids. However, methodological limitations such as confounding by indication due to the choice of non-use as comparator render the interpretation of most of these studies difficult. Thus, further efforts in preclinical research and well-conducted observational studies are needed to provide more robust evidence in this regard.