Abstract Objective This study aimed to investigate the role of environmental pollutants, specifically nitrogen dioxide (NO2) and particulate matter (PM10), on children and young adults (CYA) living with sickle cell disease (SCD) in the United Kingdom. Given the heightened vulnerability of this population due to socio-environmental factors, we explored how these pollutants influence hospitalization rates, sleep quality, and cognitive function. Methods Data were analyzed from the London Sleep Asthma Cohort, which included 94 CYA living with SCD at Visit 1, although this full sample was not available for all analyses. Participants’ exposure to NO2 and PM10 was determined using air quality data linked to their residential postcodes. Hospitalizations, sleep quality, and cognitive function were assessed through medical records, caregiver questionnaires, and cognitive testing. Multiple regression analyses were conducted to determine the relationship between pollutant exposure and health outcomes, controlling for age, community deprivation, and asthma diagnosis. Results The study found that NO2 exposure significantly predicted lifetime hospitalizations for acute chest syndrome (ACS), particularly among participants with asthma. However, despite some trends toward significance, no significant relationships were observed between pollutant exposure and pain-related hospitalizations, sleep quality, or cognitive function. Conclusions Our preliminary findings suggest that NO2 exposure exacerbates respiratory complications in CYA with SCD, especially in those with asthma. Our results underscore the need for targeted public health interventions to mitigate air pollution in marginalized communities, which could reduce ACS-related hospitalizations and improve health outcomes for vulnerable populations. Further research is recommended to explore the mechanisms linking pollution to SCD complications.