The objective was to study the role of serum immunoglobulin levels, mannose-binding lectin (MBL), and Fc gamma receptor (Fc R) polymorphisms on the development of recurrent otitis media with effusion (OME). Children aged between two and seven years with persisting OME received bilateral tympanostomy tubes and immunological parameters were investigated in relation with OME recurrence within six months after tube extrusion. No statistically significant differences in serum immunoglobulin levels were present between children with and without OME recurrence. In children with bilateral recurrence (n = 56), median levels of MBL were 1.39 mg/L compared to 2.48 mg/L in children with OME recurrence (n = 17) (p = 0.29). In addition, 34% of the children with bilateral recurrence were homozygous for the genotype Fc RIIa-R/R131, whereas less than 20% of the children with unilateral recurrence or those without recurrence were homozygous for this Fc receptor (p = 0.26). Serum mannose-binding lectin and Fc RIIa-R/R131 polymorphism may play a role in the aetio-pathogenesis of recurrent OME.