This paper examines, conceptually, the relationship between stress-inducing architectural features and allostatic overload 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. While there is evidence from the field of neuroarchitecture that short-term exposure to particular architectural features produce acute stress responses, there is yet to be a study on the relationship between stress-inducing architectural features and allostatic load. This paper considers how to design such a study by reviewing the two primary methods used to measure allostatic overload: biomarkers and clinimetrics. Of particular interest is the observation that the clinical biomarkers used to measure stress in neuroarchitectural studies differ substantially from those used to measure allostatic load. Therefore, the paper concludes that while the observed stress responses to particular architectural forms may indicate allostatic activity, further research is needed to determine whether these stress responses are leading to allostatic overload. Consequently, a discrete longitudinal public health study is advised, one which engages the clinical biomarkers indicative of allostatic activity and incorporates contextual data using a clinimetric approach.