This systematic review indicates that hydroxyurea may be a promising pharmacologic option for leukoreduction in paediatric critical pertussis. In reported cases, hydroxyurea was associated with leukocyte reduction and short-term survival. Its ability to potentially reduce the need for invasive leukoreductive procedures is especially relevant in resource-limited settings. While these observations are encouraging, the evidence base remains limited to a small number of uncontrolled case reports and case series, with inconsistent safety monitoring and no long-term follow-up. Given the very low certainty of the available evidence, these results should be considered preliminary and hypothesis-generating. Further well-designed, multicentre studies and randomised trials are urgently needed to confirm whether hydroxyurea can fulfil its potential as an effective and safe adjunctive treatment for this high-risk population.