22Hormones such as glucocorticoids (colloquially referred to as "stress hormones") have important 23 effects on animal behavior and life history traits, yet most of this understanding has come through 24 correlative studies. While experimental studies offer the ability to assign causality, there are important 25 methodological concerns that are often not considered when manipulating hormones, including 26 glucocorticoids, in wild animals. In this study, we examined how experimental elevations of cortisol 27 concentrations in wild North American red squirrels (Tamiasciurus hudsonicus) affected their 28 hypothalamic-pituitary-adrenal (HPA) axis reactivity, and life history traits including body mass, litter 29 survival, and adult survival. The effects of exogenous cortisol on plasma cortisol concentrations 30 depended on the time between treatment consumption and blood sampling. In the first nine hours after 31 consumption of exogenous cortisol, individuals had significantly higher true baseline plasma cortisol 32 concentrations, but adrenal gland function was impaired as indicated by their dampened response to 33 capture and handling and to injections of adrenocorticotropic hormone compared to controls. 34 Approximately 24 hours after consumption of exogenous cortisol, individuals had much lower plasma 35 cortisol concentrations than controls, but adrenal function was restored. Corticosteroid binding globulin 36 (CBG) concentrations were also significantly reduced in squirrels treated with cortisol. Despite these 37 profound shifts in the functionality of the HPA axis, squirrel body mass, offspring survival, and adult 38 survival were unaffected by experimental increases in cortisol concentrations. Our results highlight that 39 even short-term experimental increases in glucocorticoids can affect adrenal gland functioning and CBG 40 concentrations but without other side-effects.41 42 103increased body mass in squirrels (Axelrod, 1976), but did not expect our treatment dosages to be 104 sufficiently high to cause anorexia through sustained adrenal impairment (Arlt and Allolio, 2003). As we 105 aimed to keep GCs within a physiologically-relevant ('normal') range for this species, we did not expect 106 to see negative effects of our treatments on body mass or adult or litter survival. 107 108 109 6