OBJECTIVE We aimed to evaluate clinical and laboratory characteristics of children with preseptal cellulitis (PC) and orbital cellulitis (OC) and also to determine whether clinical and/or laboratory parameters could be used to distinguish OC from PC. METHODS The medical records of pediatric patients (aged between 1 month and 18 years) with PC and OC who had been hospitalized at our center from January 2008 to December 2020 were retrospectively reviewed. Multivariable regression analysis was performed to identify possible parameters useful in differentiating between PC and OC. RESULTS A total of 375 patients [202 (53.9%) boys], of whom 35 (9.3%) had OC, were evaluated. Median age was 44 (range, 1-192) months. Compared to those with PC, patients with OC were older (p = 0.001), had fever, upper respiratory tract infection (URTI) symptoms, and sinusitis more frequently, and demonstrated prolonged symptom and hospitalization times (p ˂ 0.001 for all). Significant differences between groups were observed for numerous laboratory parameters; however, multivariable regression analysis revealed that only C-reactive protein (CRP) and platelet count could be used to predict OC among the laboratory findings. Taken together, factors independently associated with OC diagnosis were proptosis, ophthalmoplegia, age (>35 months), CRP level (˃116.5 mg/L), and platelet count (˃420.5 × 103/mm3). CONCLUSIONS In addition to showing previously known properties of OC versus PC, our study demonstrated that combined demographic, clinical and laboratory factors such as being aged above 35 months, having a CRP level of ˃116.5 mg/L, and platelet count of ˃ 420.5 × 103/mm3 could be used to distinguish OC from PC.