ABSTRACT Background More than 90% of all infections in the head and neck region can be traced back to an odontogenic origin. In rare cases they can lead to sepsis, which may pose a vital threat to the patient. The purpose of this study was to analyse characteristics concerning etiology and progress of severe odontogenic infections with a fulminant development. Methods All patients with odontogenic infections requiring hospital admission were included in a retrospective analysis conducted from 02/2012 to 09/2017. Of 483 patients 16 patients (13 male, 3 female) showed severe exacerbation with septic progress. The average age was 52.8 years. All patients underwent at least one surgical procedure that involved an extraoral incision and drainage as well as high volume irrigation intraoperatively. At least one revision was required for four of the patients. Three patients showed an exceedingly severe disease progression with multiorgan dysfunction syndrome (MODS) and circulatory arrest. Antibiotic treatment was adjusted according to the results of an antibiogram and resistogram. Irrigation with saline was done several times a day. Results Sixteen patients showed odontogenic infections that spread over multiple maxillo-facial and cervical regions accompanied by septic laboratory signs. All these patients needed intensive care and a tracheostomy. The hospitalization period was 27.8 days on average. In 16 cases risk factors for the development of odontogenic abscesses like diabetes mellitus, obesity, chronic alcohol and nicotine abuse, rheumatism and poor oral hygiene were present. Intraoperative swabs showed a typical polymicrobial aerobic and anaerobic spectrum of oral bacteria, especially anaerobes and streptococci, mainly Streptocococcus viridans. Conclusion Odontogenic infections with fulminant progression should be treated based on clinical and imaging data with immediate surgical incision and drainage including elimination of odontogenic foci as well as intensified intra- and postoperative irrigation. If needed, repeat imaging followed by further incisions should be performed. Immediate antibiotic treatment adapted to the antibiogram is of utmost importance. A combination of tazobactam and piperacillin has proven to be a good first choice and can be recommended for abscesses that spread over multiple levels with initial signs of severe infections.