Summary Objectives To analyse the association between self-perceived discrimination and social determinants (social class, gender, country of origin) in Spain, and further to describe contextual factors which contribute to self-perceived discrimination. Methods Cross-sectional design using data from the Spanish National Health Survey (2006). The dependent variable was self-perceived discrimination, and independent and stratifying variables were sociodemographic characteristics (e.g. sex, social class, country of origin, educational level). Logistic regression was used. Results The prevalence of self-perceived discrimination was 4.2% for men and 6.3% for women. The likelihood of self-perceived discrimination was higher in people who originated from low-income countries: men, odds ratio (OR) 5.59 95% confidence interval (CI) 4.55–6.87; women, OR 4.06 (95% CI 3.42–4.83). Women were more likely to report self-perceived discrimination by their partner at home than men OR 8.35 (95% CI 4.70–14.84). The likelihood of self-perceived discrimination when seeking work was higher among people who originated from low-income countries than their Spanish counterparts: men, OR 13.65 (95% CI 9.62–19.35); women, OR 10.64 (95% CI 8.31–13.62). In comparison with Spaniards, male white-collar workers who originated from low-income countries OR 11.93 (95% CI 8.26–17.23) and female blue-collar workers who originated from low-income countries (OR 1.6 (95% CI 1.08–2.39) reported higher levels of self-perceived discrimination. Conclusions Self-perceived discrimination is distributed unevenly in Spain and interacts with social inequalities. This particularly affects women and immigrants.