Objective To explore the expression of peripheral blood Nod-like receptor protein 3 （NLRP3） inflammasomes， serum caveolin-1 （Cav-1）， and sphingosine 1-phosphate receptor 1 （S1P1） in children with Kawasaki disease （KD）， and to elucidate their associations with coronary artery lesion （CAL）. Methods A total of 223 children diagnosed with KD were recruited from our hospital between March 2023 and December 2024 and served as the KD study group. These children were classified into the CAL group （n = 71） and the non-CAL group （n = 152） based on their CAL status. Additionally， 223 healthy children who underwent physical examinations at our hospital were selected as the healthy control group. Clinical data， levels of routine laboratory test indices， peripheral blood NLRP3 inflammasomes， serum Cav-1， and S1P1 were compared among the groups. Risk factors for CAL in children with KD were analyzed， and the diagnostic value of peripheral blood NLRP3 inflammasomes， serum Cav-1， and S1P1 levels for CAL in children with KD was evaluated. Results The levels of NLRP3， caspase-1， ASC in peripheral blood and messenger ribonucleic acid （mRNA） of serum Cav-1 were significantly higher in the KD study group than in the healthy control group （P < 0.05）. Conversely， the serum level of S1P1 was significantly lower in the KD study group compared to the healthy control group （P < 0.05）. In the CAL group， the levels of peripheral blood white blood cell count （WBC）， NLRP3， caspase-1， ASC mRNA， serum C-reactive protein （CRP）， and Cav-1 were all higher than those in the non-CAL group （P < 0.05）， while the serum level of S1P1 was lower than that in the non-CAL group （P < 0.05）. The levels of NLRP3， caspase-1， ASC mRNA in peripheral blood， along with serum Cav-1 and S1P1， were identified as independent risk factors for CAL in children with KD （P < 0.05）. The results of receiver operating characteristic （ROC） analysis indicated that the combined test of the levels of NLRP3， caspase-1， ASC mRNA in peripheral blood， serum Cav-1， and S1P1 for diagnosing CAL in children with KD had an area under the curve （AUC） value of 0.926. This value was significantly higher than that of each individual index （0.844， 0.785， 0.821， 0.843， 0.833， P < 0.05）. Conclusions The levels of NLRP3 inflammatory vesicles in peripheral blood and serum Cav-1 were highly expressed in children with KD， whereas the serum S1P1 was poorly expressed. These indices may be involved in the development process of CAL in children with KD. Moreover， the combination of these indices is more beneficial for the diagnosis of CAL in children with KD.