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Background and Aim: The present study aimed to evaluate the anxiety, depression, and fear in people with and without diabetes during the transmission of the SARS-CoV-2 Omicron variant. Methods: In this comparative study (n= 353), people with diabetes (n= 121) and those without diabetes (n= 232) were investigated for physiological aspects of COVID-19 during the SARS-CoV-2 Omicron variant outbreak. This study was performed at the Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. On request, the participants responded to the survey questionnaires, providing data on demographics, Generalized Anxiety Disorder (GAD-7), and Patient Health Questionnaire-2 (PHQ-2) to screen for anxiety, depression, and COVID-19-related fears. Results: The GAD statement revealed a significantly higher degree of nervousness and anxiety among people with diabetes when compared to people without diabetes (P = 0.001). For the other GAD statements, no statistical difference was observed between the responses of people with and without diabetes, including the overall GAD-7 (P = 0.091). The PHQ-2 statement, concerning a feeling of depression or hopelessness noted a significant escalation among diabetes compared to nondiabetes (P = 0.004). Furthermore, in the overall PHQ-2, a significant escalation (P = 0.011) was noticed among people with diabetes compared to nondiabetes. In addition, people with diabetes had a significantly high (P = 0.037) COVID-19-related fear reported, compared to people without diabetes. Conclusion: The need for comprehensive research is urgent, as it will facilitate a better understanding of the physiological aspects of COVID-19 for patients with diabetes.