We longitudinally examined the influence of anti-tumor necrosis factor (TNF)-α treatment on serum levels of KL-6 and surfactant protein-D (SP-D). The study group comprised 22 patients with psoriasis treated with infliximab or adalimumab and with no history of interstitial lung disease (ILD). KL-6 and SP-D levels were measured in serum samples. Twelve of the 22 patients (55%) showed at least a 20% increase in KL-6 levels compared with baseline. Of these 12 patients, none exhibited any signs of ILD on chest computed tomography and nine who showed an increase in KL-6 levels (75%) showed at least a 20% increase in SP-D levels. Some patients showed simultaneous increases in KL-6 and SP-D levels after treatment with anti-TNF-α agents. Although these patients may have undetectable or subtle alveolar damage, careful observation is needed.