Objectives: This study aims to study the healthcare (HC) costs associated with cystic fibrosis (CF) in children diagnosed prenatally (ANT), through newborn screening (NBS), after birth due to meconium ileus (MI), or later based on symptoms (LS). Additionally, it seeks to clinically characterize children with CF (chCF) with different trajectories of HC costs. Study design: A retrospective observational study was conducted on data from the French CF Registry (FCFR) and the French National Claims Database (SNDS) linked from 2006 to 2021. HC costs related to CF diagnosis circumstances were estimated per year of life among chCF up to age 10. Group-based trajectory modeling was performed to identify subgroups with similar cost trajectories. Results: Between 2006 and 2011, data from 1,065 chCF were recorded in the FCFR. 973 (91.4%) were matched with SNDS, and 779 (73.1%) had at least 10 years of follow-up. NBS resulted in the lowest costs. During the first year, HC costs of chCF diagnosed with MI and ANT were higher than for those diagnosed with NBS or LS. Expenses declined in the second year of life and then gradually increased to approximately €20,000 by the tenth year. Three groups with different cost trajectories were identified. Groups with the highest costs had a lower lung function at 6 and 10 years and the lowest weight and height z-scores at 2 and 10 years (all p<0.05). Conclusion: HC costs were lower in chCF diagnosed by NBS, and high HC costs could occur at the earliest stages of CF.