The COVID-19 pandemic has had a profound psychological impact on healthcare workers worldwide, including midwives across various levels of the healthcare system. This study aims to evaluate the psychological strain experienced by midwives in the region of Thessaly, Greece, due to the pandemic. Specifically, it examines levels of burnout while considering perceived stress, depression, and psychological resilience, as well as demographic, socio-economic, and occupational factors. This epidemiological study explores the extent of psychological distress among midwives in Thessaly during the COVID-19 crisis. Data collection was conducted between February and March 2021, involving 102 midwives, with a primary focus on burnout symptoms. Data were collected from three electronic databases: PubMed, MEDLINE, and PsycINFO. Information was gathered through a structured questionnaire covering sociodemographic and professional characteristics, alongside validated assessment tools, including the Spielberger State-Trait Anxiety Inventory, the Connor–Davidson Resilience Scale, the Beck depression inventory, and the Copenhagen Burnout Inventory. Statistical analysis was conducted using multifactorial linear regression to identify factors influencing midwives’ mental health during the pandemic. Midwives experiencing high stress and burnout had an increased risk of depression, whereas psychological resilience was identified as a crucial protective factor against depressive symptoms. Midwives in Thessaly, Greece, have faced substantial psychological distress, with their overall mental well-being significantly impacted by the COVID-19 pandemic. These findings emphasize the need for targeted psychological support and preventive interventions for midwives, particularly in ongoing or future public health crises.