Acute chest syndrome (ACS) is a common lung complication associated with high morbidity and mortality in children with sickle cell disease. The role of fine particulate matter (PM 2.5) exposure in admissions for ACS is limited. We assessed residential level PM 2.5 exposure in a case-crossover study of 503 patients admitted to Texas Children’s Hospital between 2010 and 2019 in Houston, TX. We examined whether short-term PM 2.5 exposure is associated with increased odds of hospitalizations for ACS and found no association between PM 2.5 exposures in the week proceeding an ACS-related admission. However, larger studies are needed to confirm or refute this finding.