To provide reliable, effective immobilization for Weddell seals under extreme field conditions using an injectable ketamine/midazolam combination. Observational study. Thirty adult Weddell seals (12 male, 18 female) in Erebus Bay, Antarctica, body mass (mean ± SD) 412 ± 47 kg, aged 9–27 years. Seals were immobilized with a target dose of 2 mg kg−1 ketamine hydrochloride and 0.1 mg kg−1 midazolam hydrochloride (IM), based on visually estimated body mass. When required, maintenance doses were administered at a target of 0.5 mg kg−1 ketamine hydrochloride and 0.025 mg kg−1 midazolam hydrochloride (IV). Complete immobilization was achieved in 33 of 40 injections (14 of which were repeat events on the same individual). Time to immobilization averaged 12 ± 4 minutes, with a duration of initial immobility of 38 ± 19 minutes. Total immobilization time varied by handling protocol, including condition assessment and muscle biopsy (Protocol 1, 60 ± 13 minutes), condition assessment and instrument attachment (Protocol 2, 154 ± 13 minutes), and condition assessment, muscle biopsy and instrument retrieval (Protocol 3, 48 ± 8 minutes). Overall, a total immobilization time of 114 ± 60 minutes was accomplished with 4 ± 4 maintenance doses, and an average recovery time of 36 ± 17 minutes. Most effects of the anesthetic combination were unrelated to mass, age, sex or total body fat. However, leaner seals had longer duration of initial immobility (% and kg total body fat) and recovery times (kg fat). Apnea events were uncommon and treated effectively with doxapram. No animals died. Reliable and effective field immobilization of Weddell seals was accomplished with a low dose of ketamine hydrochloride and midazolam hydrochloride, utilizing IM injection initially and IV maintenance methods.