Injection site reactions (ISRs) are quite common side effects defined by a local adverse drug reaction directly caused by a vaccine. Twenty-four hours after an intramuscular injection (in the deltoid muscle) of the diphtheria, tetanus, acellular pertussis, inactivated poliomyelitis, Haemophilus influenza type b (DTPCa-Hib) combined vaccine, a 3-year-old boy developed fever. A few hours later, local redness and swelling appeared at the injection site, with rapid extension to the entire limb, it was pain-free, and no other clinical anomalies were present. The patient received intravenous antibiotics for suspected cellulitis. The progression was favorable in 12h (apyrexia and decreased limb swelling), allowing the intravenous antibiotic treatment to be discontinued. Since the child was in excellent general health and recovery was fast, an ISR was diagnosed. Extensive limb swelling is frequent, mostly after the fourth dose of DTPCa-Hib. Deltoid muscle injection of DTP vaccine increases the risk of ISR compared to injection in the thigh, before the age of 3 years. The introduction of acellular pertussis vaccine decreased the risk of general side effects but may increase the risk of ISR. These reactions disappear with symptomatic treatment and do not contraindicate the product.