Background Increased levels of soluble E-selectin (sE-selectin) and soluble intercellular cell adhesion molecule-1 (sICAM-1) have been reported in patients with psoriasis vulgaris compared with controls. Objective The aim of this study was to investigate the effects of narrow-band ultraviolet-B (NB-UVB) phototherapy on sE-selectin and sICAM-1 serum levels in patients with psoriasis vulgaris. Patients and methods This case–control study included 30 patients with psoriasis vulgaris and 20 apparently healthy participants as a control group. Both patients and controls were subjected to full history taking, dermatological examination, and measurement of sE-selectin and sICAM-1 using enzymelinked immunosorbent assay kits. In the patient group, sE-selectin and sICAM-1 were measured after treatment with NB-UVB phototherapy, and the response was assessed by the Psoriasis Area and Severity Index (PASI) score. sE-selectin and sICAM-1 serum levels were compared before and after treatment and correlated with PASI scores. Results In this study, sE-selectin and sICAM-1 serum levels were significantly higher in the patient group than in the control group (P = 0.001 for both). There were statistically significant reductions in sE-selectin and sICAM-1 serum levels after NB-UVB phototherapy (P = 0.001 for both), but still the levels were higher than those of controls. PASI scores significantly decreased after treatment, confirming the efficacy of NB-UVB phototherapy. Both sE-selectin and sICAM-1 serum levels were positively correlated with PASI scores before and after NB-UVB phototherapy (P = 0.001 for both). Conclusion The present study emphasizes the complex nature of the roles played by cell adhesion molecules in the immune-pathogenesis of psoriasis and the effect of NB-UVB phototherapy on their values in relation to the PASI score. Also, results of this study provide a rationale for the possible application of sE-selectin and sICAM-1 measurements as biomarkers of psoriasis activity and predictors of possible exacerbation.