The anti-inflammatory and analgesic effects of B vitamins have been already demonstrated. It seems that these agents are effective in treating knee osteoarthritis (KOA), which is associated with an inflammatory status of the joint. However, the available documents showing the efficacy of these vitamins are so limited. In the current study, we investigated the effects of B vitamins on pain relief and function improvement in patients with KOA. Sixty patients with mild to moderate KOA were randomly divided into two equal groups of celecoxib (control) and celecoxib with B vitamins (neurobion). Patients were treated for two months. Before and after the treatment, patients' pain intensity and function were measured using visual analogue scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) respectively. On the last visit, the pain intensity significantly decreased and WOMAC scores significantly increased in both groups, respectively (p<0.001). However, the WOMAC scores were the same in both groups , while the pain intensity was significantly lower in neurobion group on the last visit (p<0.001). Our findings showed that prescribing B vitamins can effectively exacerbate the analgesic effect of celecoxib in patients with KOA without any complications.