BackgroundSerum eye drops (SED) are used to treat ocular surface disease. Reactions to SED are poorly documented.MethodsWe present our experience of self‐reported reactions in New Zealand to SED (25%; autologous, allogeneic, or both) between 2003 and 2023, and a focused review of the literature.ResultsIn total, 1067 patients received SED treatment (562 autologous, 318 allogeneic, and 187 both). Three (0.5% of those treated with allogeneic SED) reported reactions. All appeared to be allergic. All were associated with allogeneic SED. We have information on two patients: one had an eye reaction; in the other, the gastrointestinal tract was involved. The literature contains few reports of reactions to SED. They have involved both autologous and allogeneic SED, and various SED concentrations. None appears to have been severe. Notably, no eye or systemic infections have been reported.ConclusionsInformation on the types and frequencies of reactions to SED is poor. This may be due to: serum being less likely to cause reactions; eyes being resistant to reactions; reactions being rare, and insufficient use of SED having occurred; under‐reporting related to SED use at home and reactions being mild. More robust monitoring for reactions to SED is needed.