Aims/Purpose: To evaluate the symptomatic and clinical efficacy and in vivo confocal microscopy (IVCM) changes of the cornea after allogeneic serum eye drop therapy in patients with Sjögren's syndrome (SS)‐related Dry Eye Disease (DED).Methods: In this prospective clinical study 15 patients (30 eyes) with primary or secondary SS‐related DED were evaluated for Ocular Surface Disease Index (OSDI) questionnaire, ocular inflammation grade, Schirmer's test, tear film break‐up time (TBUT), corneal and conjunctival staining, and in vivo confocal microscopy (IVCM) analysis.Results: The average age of patients was 63.87 ± 9.18 years. The patients received treatment for a mean of 81.13 ± 56.84 days. The difference between before and after treatment with allogeneic serum eye drop therapy was statistically significant for OSDI parameters (p = 0.001), ocular inflammation (p = 0.004), TBUT (p = 0.007), Oxford Staining Scale (p = 0.007), Van Bijsterveld score (p = 0.006), basal epithelium density (p = 0.005), intermediate epithelium density (p = 0.041), Corneal Nerve Branch Density (CNBD) (p = 0.040), Beadings density (p = 0.047) and Fibre Tortuosity (p = 0.002).Conclusions: Allogeneic SEDs treatment in SS related DED patients, showed great results in terms of improvement in dry eye symptoms, clinical signs and IVCM changes. Further studies that aim at propagating and standardizing its production with clear international guidelines are needed.