Summary Reasons for performing study: Continuous‐rate infusions (CRI) of lidocaine are often used for prolonged duration but, to date, only limited time/concentration relationships administered as a short term (24 h) CRI have been reported. Objective: To determine the time/concentration profile of lidocaine and its active metabolites glycinexylidide (GX) and monoethylglycinexylidide (MEGX) during a 96 h lidocaine infusion. Methods: Lidocaine was administered to 8 mature healthy horses as a continuous rate infusion (0.05 mg/kg bwt/min) for 96 h. Blood concentrations of lidocaine, GX and MEGX were determined using high performance liquid chromatography during and after discontinuation of the infusion. Results: Serum lidocaine concentrations reached steady state by 3 h and did not accumulate thereafter. Concentrations were above the target therapeutic concentration (980 ng/ml) only at 6 and 48 h, and did not reach the range described as potentially causing toxicity (>1850 ng/ml) at any time. MEGX did not accumulate over time, while the GX accumulated significantly up to 48 h and then remained constant. The serum concentrations of lidocaine, MEGX and GX were below the limit of detection within 24 h of discontinuation of the infusion. None of the horses developed any signs of lidocaine toxicity during the study. Conclusions: The metabolism of lidocaine was not significantly impaired by prolonged infusion and no adverse effects were observed. Prolonged infusions appear to be safe in normal horses but the accumulation of GX, a potentially toxic active metabolite, is cause for concern. Clinical relevance: Although the toxic level of GX has not yet been determined, such accumulation could lead potentially to adverse side effects and it is important to consider this potential for accumulation when utilising prolonged lidocaine infusions.