This paper examines the relationship between stress-inducing architectural features and allostatic overload (i.e. metabolic instability) by drawing on literature from neuroimmunology and neuroarchitecture. The studies reviewed from the field of neuroimmunology indicate that chronic or repeated exposure to stress-inducing events may overwhelm the body’s regulatory system, resulting in a process termed allostatic overload. There is evidence from the field of neuroarchitecture that short-term exposure to particular architectural features produce acute stress responses. The paper calls for additional research on the impacts of long-term stress on health, including neuroinflammatory diseases.