Purpose <p>While the use of antibiotics could increase the development of antibiotic-resistant microorganisms, yet, it is a standard protocol in some hospitals. Therefore, the purpose of this study was to debate this protocol by assessing the effects of prophylactic antibiotics in paediatric dental rehabilitation under general anaesthesia.</p> Methods <p>This is a quasi-study comparing existing healthy (<i>n</i> = 46) children aged between 3 and 6 years at two hospitals in Saudi Arabia to assess the effects of prophylactic antibiotics in paediatric dental rehabilitation under general anaesthesia. The infection condition was identified by measuring fever, and periapical lesions.</p> Results <p>No significant differences were reported in both terms. Infections in terms of fever (<i>P</i> = 0.295), the results revealed that 95.7% of children in the antibiotic group had no infections, whereas in the no-antibiotic group, 87% showed no infections. In terms of periapical lesions, 87.0% of the first group exhibited no periapical lesions (<i>P</i> = 0.343), while 8.7% had “1” (vertical bone defects or both), and 4.3% fell into the “2” category. Similarly, in the control group, 87.0% showed no periapical lesions, while 13.0% had infections.</p> Conclusion <p>Within the limitations of the present quasi-study in two Saudi-Arabian hospitals, it has been shown that although prophylactic antibiotics are still routine in some hospitals, their use is not justified in paediatric dental rehabilitation under general anaesthesia. Updating the relevant protocols in such operations is strongly recommended.</p>