Background Chemical immobilization of Weddell seals (Leptonychotes weddellii) has previously been, for the most part, problematic and this has been mainly attributed to the type of immobilizing agent used. In addition to individual sensitivity, physiological status may play an important role. We investigated the use of the intravenous administration of a 1:1 mixture of tiletamine and zolazepam (Telazol®) to immobilize adult females at different points during a physiologically demanding 5–6 week lactation period. We also compared performance between IV and IM injection of the same mixture. Results The tiletamine:zolazepam mixture administered intravenously was an effective method for immobilization with no fatalities or pronounced apnoeas in 106 procedures; however, there was a 25 % (one animal in four) mortality rate with intramuscular administration. Induction time was slightly longer for females at the end of lactation (54.9 ± 2.3 seconds) than at post-parturition (48.2 ± 2.9 seconds). In addition, the number of previous captures had a positive effect on induction time. There was no evidence for effects due to age, condition (total body lipid), stage of lactation or number of captures on recovery time. Conclusion We suggest that intravenous administration of tiletamine and zolazepam is an effective and safe immobilizing agent for female Weddell seals. Although individual traits could not explain variation in recovery time, we suggest careful monitoring of recovery times during longitudinal studies (> 2 captures). We show that physiological pressures do not substantially affect response to chemical immobilization with this mixture; however, consideration must be taken for differences that may exist for immobilization of adult males and juveniles. Nevertheless, we recommend a mass-specific dose of 0.50 – 0.65 mg/kg for future procedures with adult female Weddell seals and a starting dose of 0.50 mg/kg for other age classes and other phocid seals.