Background: Previous studies have assessed the relative importance of material, psychosocial and behavioural factors in the explanation of relative socio-economic inequalities in mortality, but research into the contribution of biomedical factors has been limited. Our study examines the relative contribution of (i) material, (ii) psychosocial, (iii) behavioural and (iv) biomedical factors in the explanation of relative socio-economic (educational and income) inequalities in mortality. Methods: Cohort study—baseline data from the Norwegian total county population-based HUNT 2 study linked to mortality data (1995/97 to 2003). In this analysis, 18 247 men and 18 278 women aged 24–80 without severe chronic disease at baseline were eligible. Results: No socio-economic inequalities in mortality among women were found. In men, educational- and income-related inequalities in mortality were found with a relative risk for the lowest educational group of 1.67 (1.29–2.15) and the lowest income quartile of 2.03 (1.57–2.70). Together, the four explanatory factors reduced the relative risk of mortality of the lowest educational group to 1.18 (0.90–1.55) and the relative risk of mortality in the lowest income quartile was attenuated to 1.17 (0.83–1.63). Known biomedical factors contributed least to both educational and income inequalities in mortality. Conclusions: Material factors were the most important in explaining income inequalities in mortality amongst men, whereas psychosocial and behavioural factors were the most important in explaining educational inequalities. This suggests that improving the material, psychosocial and behavioural circumstances of men might bring more substantial reductions in relative socio-economic inequalities in mortality.