The sympathetic nervous system plays a crucial role in metabolic function and glucose homeostasis. Norepinephrine is the main neurotransmitter released from sympathetic neurons. The major goal of our studies was to examine the impact of norepinephrine on metabolism related gene expression in obesity in vivo. Interestingly, we discovered that norepinephrine had a detrimental effect in our studies. C57BL6/J mice fed a high fat diet were intraperitoneally injected with 0.2 or 2 mg/kg/day norepinephrine. These doses of norepinephrine have been used previously by other researchers. Survival of the mice was documented. Kidney and bladder tissues were excised and fixed for histological studies. A subset of norepinephrine treated mice experienced unexpected adverse events which included bladder distension and reduced kidney perfusion as suggested by kidney discolouration. This eventuated in the mice having to be sacrificed or the mice succumbed to the pathological condition. To our knowledge, such an effect of norepinephrine has not been previously reported in mice. Morphological examination of kidney and bladder indicated marked detrimental architectural changes, which we postulate is associated with norepinephrine induced vasoconstriction, urinary retention and renal impairment. Our studies highlight that administration of norepinephrine to mice may trigger adverse effects relating predominantly to the urogenital tract which can result in decline in a subpopulation of these mice. Researchers administering norepinephrine in mouse models should be aware and look out for these unexpected adverse events associated with the use of norepinephrine.