Uganda´s well-being ranks among the worst in the world, while Sweden´s well-being ranks among the best. This thesis investigates if there is a difference in well-being and dispositional optimism in Uganda and Sweden. The neurobiology underlying well-being and optimism is also examined. The neural correlations of well-being and optimism are connected to areas in the limbic system and cerebral cortex. Prefrontal cortex and anterior cingulate cortex are two curial regions involved in both well-being and optimism. Amygdala, parahippocampal gyrus, and thalamus are central areas for hedonic well-being, dispositional optimism, and optimism bias. In this thesis 284 Ugandans and 256 Swedes completed a questionnaire based survey. Greater hedonic well-being was found among Swedes, whereas greater eudiamonic well-being was found among Ugandans. Swedes reported greater global life satisfaction than Ugandans, but Ugandans expressed higher satisfaction with their current lives compared with Swedes. In relation to dispositional optimism, Ugandans were found to be both more optimistic and more pessimistic than Swedes. This unexpected dispositional optimism pattern is discussed and future research directions are proposed.