The experience of an infertility diagnosis and treatment imposes a profound burden on affected individuals, encompassing not only physical and medical aspects but also a plethora of psychological, social, and emotional factors. By employing a multimodal assessment featuring validated self-report questionnaires, physical measurements, and clinical records, the present study aimed to explore the quality of life and psycho-emotional distress of men undergoing infertility treatment in Serbia, thereby addressing the dearth of research on the underrepresented male perspective in this domain. Findings revealed diverse semen abnormalities among participants (n = 96, average age 37.69 ± 5.72), with significant associations between longer treatment durations and reduced sperm motility. The observed rates of men surpassing predetermined DASS-42 questionnaire thresholds for depression, anxiety, and stress in the analyzed cohort were 13.54%, 11.46%, and 22.92%, respectively. Summary scores in conceptual areas comprised in the SF-36 questionnaire ranged from 49.00 ± 6.25 for the mental health dimension to 90.16 ± 17.75 obtained in the physical functioning subscale. Patients with a longer treatment duration demonstrated lower scores in the role emotional domain, indicative of a less favorable emotional state. Expectedly, inverse correlations were found between the SF-36 mental health score and DASS-42 subscales. By addressing the existing knowledge gap and highlighting the unique needs of infertile men, the finding of this study may contribute to a more inclusive and holistic approach to infertility research and management.