Abstract Background and objective The survival outcomes of patients with metastatic nasopharyngeal carcinoma (NPC) differ significantly between individuals. This study aimed to evaluate whether serum lactic dehydrogenase (S-LDH) level had a clinical value in predicting clinical response and survival outcome for patients with metastatic NPC. Methods S-LDH level was measured at baseline and then before every cycle of treatment in 689 NPC patients with distant metastases. Correlations of pre-treatment and post-treatment S-LDH levels to response of treatment and survival were analysed retrospectively. Results Patients with elevated values of pre-treatment S-LDH (>245 IU/L) had significantly worse survival than those with normal values of pre-treatment S-LDH (⩽245 IU/L) ( P < 0.001). Patients with elevated values of post-treatment S-LDH had worse survival compared with those with normal values of post-treatment S-LDH ( P < 0.001). Patients with normal values of pre-treatment and post-treatment S-LDH showed the highest response rate and the most favourable prognosis. Conclusion S-LDH appears to be a significant independent prognostic index in patients with disseminated NPC that should be considered in the comparison of the results achieved with different therapies and in planning new randomised clinical therapeutic trials.