Psoriasis may be worsened by stress and mood disorders. There is an increased expression of the serotonin transporter protein (SERT) in involved psoriatic skin as compared to non-involved psoriatic skin and normal skin. The aim of this study was to investigate if the increased expression of SERT in psoriasis correlates with the severity of disease, chronic stress, and depression. Biopsies from involved and non-involved skin from the back of 20 patients with chronic plaque psoriasis were immunohistochemically analysed, using a monoclonal antibody to SERT. The severity of psoriasis was assessed for each patient using the Psoriasis area and severity index (PASI). Levels of depression and chronic stress were measured using Beck's Depression Inventory (BDI) and the salivary cortisol test, respectively. A positive correlation (r = 0.53; p < 0.05) between PASI and the numbers of SERT-positive dendritic cells in the epidermis of involved psoriatic skin was determined. We also observed a negative correlation (r = -0.46; p < 0.05) between salivary cortisol ratio levels and the numbers of SERT-positive cells in the epidermis of involved psoriatic skin, indicating a correlation between SERT expression and chronic stress. The serotonergic system may be involved in the chronic inflammation evident in psoriatic skin. Through modulating the levels of SERT, there might be a therapeutic possibility for reducing chronic inflammation in psoriasis.