Boma adaptation is an important component of rhinoceros translocations to allow transition to new diets, restricted space, and quarantine for disease screening. However, up to 20% of recently captured white rhinoceros (Ceratotherium simum) do not adjust to captivity, resulting in early release or even death. The causes and physiologic consequences of maladaptation to boma confinement are poorly understood. The aim of this investigation was to evaluate hematologic and serum biochemical changes in maladapted rhinoceros compared to animals that adapted under the same boma conditions. Ninety-six white rhinoceros were captured between 2009 and 2011 in Kruger National Park, South Africa and placed in bomas prior to translocation. Weight, complete blood count, and serum biochemical panel results were recorded when rhinoceros were placed in the boma and repeated on the day of release. In this study, the mean duration of boma confinement for maladapted white rhinoceros was 13 d (range 8–16 d) compared to 89.9 d (range 39–187 d) for adapted animals. Mean weight loss between capture and release was significantly greater in maladapted rhinoceros (224.0 versus 65.9 kgs; P<0.001). Although adapted rhinoceros had statistically significant changes in some hematologic and biochemical values, most were not considered clinically relevant. In contrast, the maladapted rhinoceros had significant changes at the time of early release from the boma, including evidence of leukocytosis with left shift, lymphopenia, eosinopenia, decreased red blood cell count and hematocrit, increased serum creatine kinase, and decreased serum calcium, phosphorus, and magnesium values. Along with loss of body condition, these findings were consistent with a stress-associated catabolic response. These changes occurred in the first 2 wk of confinement, and the results provide a foundation for evaluating adaptation in white rhinoceros. Future studies should focus on factors that improve adaptation and welfare of recently confined free-ranging white rhinoceros.