Background: There is inconsistency in the literature regarding the nature of hypothalamic-pituitary-adrenal (HPA) axis functionality in post-traumatic stress disorder (PTSD). Purpose: The review aimed to investigate HPA axis functionality via the diurnal profile of cortisol as it relates to PTSD. Methods: The authors conducted a systematic review of the literature from June 2017 – March 2019 in accordance with The PRISMA Statement in the following four databases: PubMed, MEDLINE, ScienceDirect and PsycINFO with Full Text. The search strategy was limited to articles in English language, published in peer-reviewed journals within the last decade and human studies. Search terms included “post-traumatic stress disorder” OR “PTSD”, AND “hypothalamic pituitary adrenal axis” OR “HPA axis” AND “diurnal cortisol” OR “cortisol”. PTSD sufferers of all trauma types, genders and socioeconomic statuses were included provided there was a “healthy” control group and an inclusion of reporting on inter-group measurements of diurnal cortisol profiles as a portrayal of HPA axis functionality. Results: A total of 10 studies met the criteria for inclusion in this review. The association between HPA axis functionality and PTSD was evaluated by the measurement of salivary and/or plasma cortisol concentrations. Only two studies demonstrated an association between PTSD and diurnal cortisol when compared with respective control groups while three studies found no associations. The remaining five studies found partial, mostly negative associations between PTSD and diurnal cortisol. Conclusion: Despite some indications of an association between PTSD and dysregulated HPA axis functionality as demonstrated by diurnal cortisol output, the current review has revealed mixed findings. As such, a complete understanding of HPA axis dysregulation as it relates to PTSD remains unestablished. Given the findings, further investigation into the relationship between PTSD trauma-exposed and non-PTSD trauma-exposed individuals and diurnal cortisol is warranted.