We immobilized individuals of two species of free-ranging South American foxes, including 28 chilla foxes (Pseudalopex griseus; 13 males and 15 females) and five culpeo foxes (Pseudalopex culpaeus; four males and one female). Animals were trapped and chemically immobilized with ketamine and medetominide (K-M), ketamine and xylazine (K-X), or tiletamine–zolazepam (Z). Heart and respiratory rates, hemoglobin oxygen saturation (SpO2), rectal temperature, and palpebral and anal reflexes were measured at 5-min intervals. Data were analyzed to compare the effect of anesthetic combinations on induction and recovery times, body reflexes, and physiological variables over time. In both species, K-M gave the shortest induction time, followed by K-X and Z. Palpebral and anal reflexes in chilla foxes immobilized with K-M were maintained in more animals than those treated with either K-X or Z. Animals immobilized with Z had higher heart and respiratory rates than those immobilized with either of the other two combinations. Rectal temperature decreased over time for all combinations. Foxes immobilized with K-M maintained a higher SpO2 than those immobilized with either K-X or with Z. All anesthetic combinations were satisfactory in inducing rapid and safe immobilization of the species studied. The anesthetic plane and the effects on physiologic parameters were better in animals immobilized with K-M than with either K-X or Z, and we recommend this anesthetic combination for use in Chilean foxes. Nevertheless, all three drug combinations used were satisfactory in inducing rapid and relatively smooth anesthesia.