Asparaginase-induced hypertriglyceridemia can have a spectrum of clinical presentations, from being asymptomatic to having life-threatening thrombosis or hyperviscosity syndrome. At present, there is no recommendation on routine lipid monitoring during asparaginase-containing treatment phase, nor a standardized guideline on its management. Two cases are presented here to illustrate the effects of concurrent infection on asparaginase-induced hypertriglyceridemia in patients with high-risk ALL and the use of SMOFlipid infusion as a treatment option in an acute situation.