Patients undergoing Roux-en-Y gastric bypass (RYGB) are at increased risk of lithium toxicity. Risk factors include pre-operative dietary changes to fluid and sodium intake, gastrointestinal tract manipulation from the surgical procedure that may alter drug absorption, and short term diet related complications. The following case report describes a woman who experienced severe lithium toxicity 4 weeks after surgery. This was despite efforts to mitigate the risk with a lithium monitoring and dose modification protocol. It is unclear whether her diet related complications led to dehydration, acute kidney injury and subsequent toxicity or if her lithium absorption increased after surgery causing toxicity and subsequent kidney injury. Regardless of the cause, further research is required to determine the impact of RYGB on the pharmacokinetic changes of high risk medications such as lithium.