The cellular landscape of the paediatric respiratory system remains largely uncharacterised and as a result, the mechanisms of globally important childhood respiratory diseases remain poorly understood. A major limitation in defining mechanisms of disease has been the availability of tissue samples collected in early life, as well as technologies that permit deep immune analysis from limited sample volumes. In this work we used high dimensional flow cytometry and inflammatory cytokine profiling to map the local (bronchoalveolar lavage - BAL) and systemic (whole blood) immune response in preschool aged children with cystic fibrosis (CF) and age-matched healthy controls. We demonstrate that children with CF show pulmonary infiltration of CD66b+ granulocytes and increased levels of MIP-1α, MIG, MCP-1, IL-8, and IL-6 in BAL relative to healthy control children. Proportions of systemic neutrophils positively correlated with age in children with CF, whilst systemic CD4 T cells and B cells were inversely associated with age. We show that inflammatory cells in the BAL from both CF and healthy children express higher levels of activation and migration markers relative to their systemic counterparts. CITE-seq analysis (transcriptome-wide single cell sequencing combined with 154 cell surface antigens) of BAL samples from children with CF revealed novel tissue-resident macrophage, infiltrating monocytes, natural killer T cell, and epithelial cell subsets in the paediatric lung. This work highlights the utility of multi-omic immune profiling and advanced analytical pipelines to understand mechanisms of lung disease in childhood, with potential to identify clinically relevant disease biomarkers.