Objective Some of the symptoms of major depressive disorder (MDD) and some aspects of quality of life (QoL) are available to effective nurse intervention. The aim of the study was to examine the association of QoL of persons diagnosed with MDD with the severity of individual symptoms available to effective nurse intervention. The purpose of the study is to understand the association of quality of life with the particular symptoms of MDD available to the nurse's intervention. Materials and Methods Unicentric, cross-sectional study was conducted on a consecutive sample of 72 participants during 2019 at the Department for Psychiatry of the University Hospital CenterSestre Milosrdnice in Zagreb. The protocol was approved by the institution's Ethics Committee, and all participants signed informed consent. The target population was outpatients with diagnosed MDD (ICD-10: F32 and F33). Inclusion criteria were: confirmed diagnosis of MDD, age 18-65 years, both genders, outpatient treatment at the Department for Psychiatry. The primary outcome was a subjective assessment of health-related quality of life as measured by the visual-analog scale of the EQ-5D-5L questionnaire. Results The study showed negative association between more intensive pessimism as well as dissatisfaction with oneself of any intensity with quality of life in persons/patients with major depressive disorder. Hypothesis regarding association between sadness and (total) quality of life was not confirmed. Conclusion It seems that medical nurse interventions that decrease patient's pessimism and dissatisfation with himself/herself (oneself), could contribute to quality of life improvement in patients with major depressive disorder.