Ten white rhinoceros (Ceratotherium simum) were immobilized for a total of 13 procedures in holding facilities in Kruger National Park using etorphine, azaperone, and hyaluronidase to assess the effect of extended immobilization on serial cardiorespiratory, blood gas, and lactate values. Butorphanol was administered intravenously following initial blood collection and physiologic assessment (t = 0). Respiratory and cardiovascular parameters, body temperature, and arterial blood gases were monitored at 10-min intervals for a total of 100 min. Initial parameters at the time of recumbency revealed severe hypoxemia, hypercapnia, tachycardia, an increased alveolar-arterial (A-a) gradient, and mildly elevated lactate levels. At 10 min and 20 min, there were significant (P < 0.05) changes in the following physiologic parameters: heart rate decreased [96 and 80 beats/min, respectively, vs. 120 beats/min], arterial partial pressure of oxygen (PaO₂) increased [48 and 45 mm Hg, respectively vs. 30 mm Hg], arterial hemoglobin oxygen saturation increased [79% and 74%, respectively, vs. 47%], A-a gradient decreased [29.13 and 30.00 mm Hg, respectively, vs. 49.19 mm Hg], and respiratory rate decreased [5 and 5 breaths/min vs. 7 breaths/min]. Blood lactate levels also decreased from 2.54 mM/L to 1.50 and 0.89 mM/L, respectively. Despite initial improvements in blood oxygen levels at t = 10 and 20 min, the rhinoceros remained severely hypoxemic for the remainder of the procedure (median PaO₂ = 50.5 mm Hg, 95% confidence interval, 43.8–58.1). Median values for respiratory rate (5 breaths/min) and arterial partial pressure of carbon dioxide (PaCO₂; 68.5 mm Hg) did not change significantly for the remaining 80 min. Median lactate, base excess, bicarbonate, and pH values improved between 20 and 100 min despite the persistent hypercapnia, indicating that the animals adequately compensated for respiratory and lactic acidosis. White rhinoceros were immobilized for 100 min with no negative effects, a desirable outcome if procedures require extended chemical immobilization without oxygen supplementation.