OBJECTIVES:  To estimate the social cost of cognitive impairment in patients with Major Depressive Disorder (MDD). METHODS:  In order to achieve the objective of the study, an analytical model was built. The model estimates the annual productivity losses due to MDD-related cognitive impairment, by relating data concerning absenteeism and presentism to patients’ cognitive function measured by a 10-point scale then converted into a Sheehan Disability Scale (SDS). Also, Montgomery-Asberg Depression Rating Scale (MADRS), a patients self-reported measure of how MDD affects the ability to work on a 7-point Likert scale, and a set of items investigating attention and task performance on a 5-point Likert scale were utilized in the sensitivity analysis. Data to populate the model come from a previous survey involving 342 working patients with MDD and investigating the impact of disease on daily life. The human capital approach has been used to express the productivity losses in monetary units, and OECD average gross income has been applied as a unitary cost. Both a deterministic and probabilistic sensitivity analyses have been run. RESULTS: In the base case the model estimated a loss of € 1.129 per patient per year attributable only to cognitive impairment. In the sensitivity analysis such a figure ranged between €1.104 and €1.464 according to the scale utilized to measure cognitive impairment. CONCLUSIONS: Major depression disorder is one of the diseases with the highest impact in Europe and worldwide. Such a disease often results in dramatic cognitive impairment generating remarkable productivity losses. This issue should be taken into account in medical decision making and when assessing the cost-effectiveness of treatment strategies.