We present a case of an 8-day-old infant boy with transient neonatal diabetes mellitus who presented to our emergency department with profound dehydration, failure to thrive, and hyperglycemia. The initial ill appearance of the patient required attention to a broad differential diagnosis including cardiac, metabolic, endocrine, and infectious processes. Transient neonatal diabetes mellitus is one of several causes of severe hyperglycemia in the neonatal period and is caused by genetic imprinting at the 6q24 region. It requires specific genetic testing for diagnosis. This case illustrates initial management of and recommended laboratory testing in neonates presenting with possible transient neonatal diabetes mellitus.