Background: Sickle cell anaemia (SCA) is a prevalent genetic disorder in sub-Saharan Africa, characterised by frequent vaso-occlusive crises and other complications. Hydroxycarbamide (hydroxyurea) has proven effective in managing SCA but is underutilised in low- and middle-income countries (LMICs) due to cost and monitoring challenges. This study aims to ascertain the impact of a fixed low-dose hydroxycarbamide regimen on emergency room visits and treatment adherence for paediatric SCA patients in a resource-limited setting. Methods: An observational study was conducted over two years (January 2022 to December 2023) in a tertiary hospital in South East Nigeria. One hundred children aged 1 to 18 years with confirmed SCA (HbSS genotype) were administered a fixed low-dose hydroxycarbamide regimen (20 mg/kg/day, capped at 500 mg/day). The primary outcome was the number of emergency room visits due to SCA-related crises. Secondary outcomes included treatment adherence and factors influencing adherence. Patients experiencing breakthrough crises had their doses increased to 25 mg/kg/day or from 500 mg to 750 mg. Results: Over the study period, only one patient (0.01%) on the fixed low-dose regimen presented to the clinical emergency room with a vaso-occlusive crisis, necessitating a dose increase. Treatment adherence was high, with 84.2% of patients reporting consistent adherence throughout the study period. Younger patients were more likely to adhere to treatment (mean age of compliant patients: 8.49 ± 5.28 years vs. non-compliant: 11.62 ± 4.21 years, p=0.027). Father’s age was also associated with adherence, with non-compliant patients having older fathers (median age 49.0 vs. 44.0 years, p=0.02). No significant clinical side effects were observed. Conclusion: The fixed low-dose hydroxycarbamide regimen significantly reduced emergency room visits and demonstrated high adherence rates among paediatric SCA patients in a resource-limited setting. This approach appears to be a safe, effective, and feasible treatment strategy for managing SCA in LMICs, potentially improving accessibility and sustainability of care.