A growing body of evidence from preclinical and clinical studies has associated alterations of the gut microbiota–brain axis with the progression and development of a number of pathological conditions that also affect cognitive functions. Spinal cord injuries (SCIs) can be produced from traumatic and non-traumatic causes. It has been reported that SCIs are commonly associated with anxiety and depression-like symptoms, showing an incidence range between 11 and 30% after the injury. These psychological stress-related symptoms are associated with worse prognoses in SCIs and have been attributed to psychosocial stressors and losses of independence. Nevertheless, emotional and mental modifications after SCI could be related to changes in the volume of specific brain areas associated with information processing and emotions. Additionally, physiological modifications have been recognized as a predisposing factor for mental health depletion, including the development of gut dysbiosis. This condition of imbalance in microbiota composition has been shown to be associated with depression in clinical and pre-clinical models. Therefore, the understanding of the mechanisms underlying the relationship between SCIs, gut dysbiosis and psychological stress could contribute to the development of novel therapeutic strategies to improve SCI patients’ quality of life.