Objective To assess the efficacy of 0.1% oclacitinib as a single agent, and in combination with tacrolimus 0.01%, for the control of ophthalmic signs of keratoconjunctivitis sicca (KCS) in dogs. Animals studied Thirty‐two dogs (57 eyes) diagnosed with idiopathic KCS were included. Inclusion criteria were Schirmer Tear Test 1 (STT‐1) values <15 mm/min and concurrent clinical signs such as ocular hyperemia and discharge. Procedures The animals were submitted to a randomized, open‐label, 5‐week study and divided into 3 treatment groups treated with the following ophthalmic solutions: (a) 0.1% oclacitinib, (b) 0.1% oclacitinib +0.01% tacrolimus, and (c) 0.01% tacrolimus. Eye drops were instilled twice daily (12‐hour intervals). At each follow‐up examination, STT‐1, clinical signs, and potential drug side effects were assessed. Results Oclacitinib did not significantly improve STT‐1 values or clinical scores. Tacrolimus alone and in combination with oclacitinib increased mean STT‐1 values by 11.84 ± 5.2 and 12.46 ± 5.3 mm/min, respectively (P = 0.0001). Clinical scores of ocular discharge and hyperemia also improved significantly in both groups receiving treatment with tacrolimus (P < 0.05). However, addition of oclacitinib to tacrolimus provided no additional improvement over tacrolimus alone. Conclusions Topical 0.1% oclacitinib twice daily is not effective in controlling the ocular signs of KCS in dogs. 0.01% tacrolimus increased STT‐1 values significantly and could potentially be used as a treatment for mild‐to‐moderate cases of KCS. Synergism between drugs did not occur, and therefore the use of oclacitinib is not justified in cases of canine KCS.