The treatment of oral and maxillofacial infections is based on a recognized algorithm that may require modification under the influence of various local and systemic factors. The aim of this study was to present a comprehensive and microbiological profile of oral and maxillofacial infections, and explore possible correlations between the course of an infection and selected systemic factors based on the medical records of 329 patients affected by the disease. We identified most common clinical, demographic, bacterial, and laboratory parameters specific for these infections. There were statistically significant differences in Erythrocyte Sedimentation Rate, number of accompanying diseases, otalgia, dyspnea, and speech difficulties occurrence and neck space involvement between diabetic and non-diabetic patients. The duration of hospitalization and accompanying diseases correlated positively with the patient age and white blood cell count, and C-reactive protein value negatively correlated with age. The primary cause of infections, age, and comorbid diseases can modify the infection course and increase the risk of developing serious complications. It confirms the need for effective and targeted bacterial treatment in the early stages of infections. Age and general diseases are the most important systemic factors determining the infection symptoms and laboratory parameters assessing the severity of the inflammatory process.