Abstract: Aim: The aim of this review is to summarize current knowledge on the interplay between immune activation and stress-response dysregulation in post-traumatic stress disorder, with particular emphasis on molecular and neurobiological mechanisms. Material and methods: This narrative review was based on a structured search of the PubMed, Scopus, and Web of Science databases, including studies published between 2010 and 2025. Keywords related to post-traumatic stress disorder, inflammation, cytokines, stress response, and neuroendocrine regulation were used. Clinical and experimental studies addressing stress–immune interactions were included. Results: Post-traumatic stress disorder is increasingly conceptualized as a systemic condition involving persistent dysregulation of neuroendocrine and immune pathways. Disturbances of the hypothalamic–pituitary–adrenal axis, including altered glucocorticoid receptor sensitivity and impaired negative feedback regulation, coexist with increased sympathetic nervous system activity. These abnormalities promote activation of pro-inflammatory transcription factors such as nuclear factor kappa B and increased production of cytokines, including interleukin-1 beta, interleukin-6, tumour necrosis factor alpha, and interleukin-18. Additional mechanisms include activation of the NLR family pyrin domain containing 3 inflammasome, oxidative stress, mitochondrial dysfunction, and microglial activation, which contribute to neuroinflammation and impaired synaptic plasticity. These processes are associated with both psychiatric symptoms and increased risk of cardiovascular and metabolic comorbidities. Conclusions: Post-traumatic stress disorder may be understood as a disorder of maladaptive stress–immune interaction. Targeting inflammatory pathways and stress-response mechanisms may improve diagnostic approaches and support the development of personalized therapeutic strategies.