We previously reported an association between relative L-ficolin deficiency and recurrent respiratory infections co-existing with allergic disorders in children. To confirm and extend this preliminary finding, we performed a prospective study on children of a similar age (mean 8.9 years) designed to establish whether the principal relationship was with infection or allergy. Serum L-ficolin values in healthy children were normally distributed with a mean value of 3838 ng/ml. L-ficolin concentrations were generally lower in patients with asthma and/or allergic rhinitis with (mean 3413 ng/ml; p=0.02) or without (3512 ng/ml; p<0.07) respiratory infections, but not in patients with respiratory infections without allergic disease (3623 ng/ml; p=0.2). The lower average values in the group comprised of children with respiratory allergy and infections were largely due to a high proportion of very low values: 18.3% had values below 2150 ng/ml compared to only 5.5% of healthy controls (OR=3.9; p=0.01). This relationship was not apparent in the groups characterized by allergy without infection or infections without allergy. An association between mannan-binding lectin (MBL) insufficiency and recurrent respiratory infections was also confirmed. One of the patients was MASP-2 deficient, evidenced both by MASP2 genotyping and by lectin pathway activity measurement. In conclusion, L-ficolin may confer some protection from microorganisms that exacerbate allergic inflammation in the lung and its relative deficiency may contribute to enhanced susceptibility to respiratory infections. MBL insufficiency and MASP-2 deficiency are risk factors for recurrence of infections independently of allergic disease.