The mammalian brain depends on a continuous supply of oxygen and glucose to meet metabolic demand. Adaptive mechanisms allow brain cells to exist under conditions of moderately low oxygen when 'idling' or exposure to high altitude as well as elevated oxygen delivery when activated. Regulation involves numerous intrinsic and extrinsic adaptive mechanisms that serve to maintain metabolic homeostasis. Under conditions of chronic low oxygen (10%) endogenous changes in CNS angiodynamics help promote survival. We questioned whether endogenous adaptation to a stressor such as mild changes in respiratory oxygen altered chronic inflammation in an animal model of multiple sclerosis (MS) experimental autoimmune encephalomyelitis (EAE). We previously reported that when mice were exposed to chronic mild hypoxia at the time of immunization with myelin oligodendrocyte glycoprotein (MOG) they exhibited a delay in disease onset and a decrease in disease severity. Changes in clinical EAE were associated with decreased T cell infiltration into the spinal cord as well as altered regulatory T-cell subsets. In this study, we examine the effect of in vivo exposure to chronic mild hypoxia after the development of disease symptoms. Mice were exposed to 10% normobaric oxygen after the clinical symptoms reach to score 2. Exposure to mild hypoxia ameliorated chronic inflammatory activity and was associated with reduction in clinical score. Further we found evidence that exposure to hypoxia increased the ratio of Foxp3+ Tregs and IL-10+ and Blimp1+ T cells following exposure to low oxygen. In addition, chronic low oxygen decreased evidence of endothelial activation.