The authors investigated the treatment outcome of patients with severe interstitial pneumonia (IP) who received opioids during end-of-life care. Twenty-two consecutive patients were retrospectively evaluated before and after continuous administration of opioids for 24 hours. All subjects died within 21 days; the mean survival period after opioid administration was 5.6 days. Six of the 22 patients (27%) died within 24 hours after opioids were initiated. In the other 16 patients, respiratory rate was significantly decreased after opioid use and there was a small, nonsignificant improvement in dyspnea measured by the Borg scale without adequate evaluation and records (n = 6). However, hypercapnia with over 10 mm Hg of Paco2 developed in two patients. Paco2 tended to be elevated after opioid use in all patients, although the change was not significant. An extremely poor outcome was attributable to the disease progression of IP in six of the patients with Pao2/FIo2 levels below 100. The other 16 patients showed both positive and negative effects as expected. Clinicians should assess dyspnea prior to opioid administration, since the purpose of the opioid administration is to relieve dyspnea. Dyspnea should be monitored and recorded in routine clinical practice, at least after hospitalization.