Purpose: Loneliness and social isolation have detrimental effects on health in old age; however, the prospective associations with quality of life (QoL) remain unclear. Furthermore, despite the existence of a European north-south gradient in the distribution of loneliness and social isolation, little is known whether the associations are context-specific. We investigated the relationships between loneliness, social isolation and QoL of older adults residing in the North (Sweden) and South (Spain) of Europe. Methods: Study sample consisted of 2995 Swedish and 4154 Spanish older adults who participated in waves six and seven of the Study on Health, Aging and Retirement in Europe (SHARE). Loneliness and social isolation were measured at the baseline, and QoL was measured at the baseline and follow-up using CASP-12. Prospective associations were assessed via multivariate linear regression. Results: In Sweden, subjects with higher vs. lower loneliness had 1.01 (95% CI: −1.55, −0.40) units lower QoL, while every standard deviation increase in social isolation was associated with a 0.27 (95% CI: −0.42, −0.09)-unit decrease in QoL. In Spain, every standard deviation increase in social isolation was associated with a 0.66 (95% CI: −1.11, −0.22)-unit decrease in QoL. The association was stronger in subjects aged ≤65 years old and those with no chronic diseases. The association with loneliness was not statistically significant in Spain. Conclusion: Loneliness and social isolation are prospectively associated with decreased QoL among older adults, yet the associations are contextually bound. Future interventions should target both exposures, among others, in order to increase QoL in this group.