Children with acute lymphoblastic leukaemia (ALL) are at increased risk of invasive pneumococcal disease. This study describes the immunogenicity of 13-valent pneumococcal conjugate vaccine (PCV13) during and after chemotherapy.Children with ALL were allocated to study groups and received a single dose of PCV13: Group 1 - maintenance chemotherapy; Group 2 - end of chemotherapy; Group 3 - 6 months after chemotherapy. A protective vaccine response was defined as at least 10 of 12 serotypes (or greater than 83% of serotypes with data) achieving post-vaccination serotype-specific IgG ≥ 0.35 µg/mL and ≥ 4 fold rise, compared to pre-vaccination at 1 and 12 months.One hundred and eighteen children were recruited. Only 12.8% (5/39; 95% CI 4.3% to 27.4%) of patients vaccinated during maintenance (Group 1) achieved a protective response at 1 month post-vaccination and none had a protective response at 12 months. For Group 2 patients, 59.5% (22/37; 95% CI 42.1% to 75.3%) achieved a response at 1 month and 37.9% (11/29; 95% CI 20.7% to 57.7%) maintained immunity at 12 months. For Group 3 patients, 56.8% (21/37; 95% CI 39.5% to 72.9%) achieved a protective response at 1 month and 43.3% (13/30; 95% CI 25.5% to 62.6%) maintained immunity at 12 months.This study demonstrated the earliest time point at which protective immunity can be achieved in children with ALL is on completion of chemotherapy. This is earlier than current recommendations and may improve protection during a period when children are most susceptible to infection.