Background: This case series discussion explores the relationship between COVID-19 and diabetes-induced immune compromise and its association with the development of Ludwig's angina, a potentially life-threatening deep neck space infection. Aim: A retrospective study which was aimed to assess the risk factors, microbiological profile, management strategies of Ludwig’s angina patients and its association with odontogenic infections and diabetes mellitus in COVID-19 pandemic. Methods: The study population consisted of 38 patients of Ludwig’s angina those presented to and were managed in the department of ENT, Government Medical College, Amritsar, Punjab, India, from January 2021 to March 2024. All the patients exhibiting clinical symptoms and signs of Ludwig’s angina were examined and a detailed history of the duration of each symptom, present and past illness, dental infection, throat infection, diabetes mellitus was taken. Results: Results: It was observed that in 60.52% cases of Ludwig’s angina history of dental infection, followed by tonsillar infection (15.78%), oral musosal injury (13.15%) and tooth extraction (10.5%). Streptococcus viridans was found in 23.68% patients, Staphylococcus aureus (13.15%), no growth in 50% cases. Major co-morbidity was diabetes mellitus (63.15%), followed by viral infections (HIV and HCV) in 15.78% and COVID-19 infections in 11.89% patients. Surgical drainage was performed in 81.57% cases including tracheostomy in 12.5% cases whereas rest treated medically. Conclusions: Ludwig’s angina should be actively treated as a surgical and medical emergency in which incision and drainage is required as early as possible. Uncontrolled diabetes mellitus delayed treatment of odontogenic infection in COVID-19 pandemic that developed Ludwig's angina and highlight the importance of early recognition and intervention to mitigate potential life-threatening complications.