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Key Clinical Message Linezolid is a potent oxazolidinone for the treatment of various gram‐positive bacterial infections. However, the drug can cause potential adverse reactions such as thrombocytopenia, hyperlactacidemia and serotonin syndrome, which warrant consideration by the medical team when planning treatment. The existing literature has reported some adverse reactions caused by linezolid, but most of these are based on clinical characteristics and simple treatment measures. Two cases of linezolid overdose resulting in thrombocytopenia, hyperlactacidemia and serotonin syndrome are presented, which were successfully managed with therapeutic drug monitoring. A dose adjustment strategy was adopted to safely and effectively mitigate linezolid‐related adverse events.