Purpose: To evaluate changes in scleral thickness in Vogt-Koyanagi-Harada (VKH) disease. Methods: This study included 34 eyes of 17 treatment-naïve patients with acute-phase VKH disease. Scleral thickness and the presence of ciliochoroidal effusion were examined using anterior segment optical coherence tomography at baseline and 1 week, 2 weeks, and 12 weeks after the start of corticosteroid treatment. Scleral thickness was measured 6 mm posterior to the scleral spur in four directions. Results: Twenty-eight eyes (82.4%) initially had ciliochoroidal effusion, but this rapidly decreased to nine eyes (26.5%) after 1 week. The sclera with ciliochoroidal effusion became thinner from baseline to 1 week at the superior (400.2 ± 46.9–353.5 ± 47.9 µm), temporal (428.4 ± 53.6–387.8 ± 56.1 µm), inferior (451.5 ± 71.0–400.5 ± 50.5 µm), and nasal (452.4 ± 78.0–407.6 ± 62.9 µm) points (P < 0.01 for all), and no further changes were observed. The sclera without ciliochoroidal effusion remained unchanged. Conclusion: In VKH disease, eyes with ciliochoroidal effusion exhibited the maximum scleral thickness during the acute phase. This thickening responded rapidly to treatment and became thinner within 1 week. Inflammation in VKH disease may affect not only the choroid but also the sclera.