Abstract Background Published studies indicate that primary cocaine users (PCUs) have a mortality rate 4–8 times higher than their age–sex peers in the general population. Most PCUs are primary intranasal cocaine users, never-injectors and never-opioid users (PICUNINOs) and are usually underrepresented in cohort mortality studies. The aim is to estimate excess mortality in all PCUs and in the subgroups of never-opioid users and PICUNINOs in Spain. Methods 714 PCUs aged 18–30 were street-recruited in 2004–2006 in Spain and followed until 2010 to ascertain vital status. Drug use was self-reported at baseline and 1–2years later. Mortality was compared with that of the general population using standardized mortality ratios (SMRs). Results SMRs were 4.7 (95% CI: 2.4–9.0), 2.5 (95%CI: 0.8–7.8) and 3.1 (95% CI: 1.0–9.6), respectively, among all participants, never-opioid users and PICUNINOS when using only baseline data on drug use, and 1.2 (95% CI: 0.2–8.5) and 1.4 (95% CI: 0.2–9.9) among the latter two subgroups, when using baseline plus follow-up data. Conclusion Short-term mortality in young Spanish PCUs is 5 times higher than in the general population. This excess mortality may largely be explained by a history of opioid use or the risk of starting such use.