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Opioids are commonly used in treating cancer pain but can cause overt toxicities like sedation, constipation and nausea. Covert toxicities such as endocrine and immune dysfunction are often unrecognised but also important to understand. Some opioids might be immunosuppressive and they might be associated with reduced survival and increased rates of infection. However, the quality of this evidence is limited and causation is unknown. There is emerging data on opioids and immunotherapies, making it even more important to understand this covert toxicity. Opioid-induced endocrinopathies, including hypogonadism, might impair quality of life and impact cancer survival. These should be assessed for in patients on long-term opioids. Hormone replacement therapies may be beneficial in specific cases. Differences opioids have variable immune and endocrine effects. Higher opioid doses might have more effect on immune and endocrine function. Ultimately, it is prudent to use the lowest effective dose to control the cancer pain.