We studied socio-cultural determinants of timely appropriate treatment seeking for children under 5 years suspected of having a perceived malaria-related illness. Caretakers of children with suspected malaria were interviewed about illness-related experiences, meanings and behaviour in two endemic villages in southern Ghana. Only 11% of children suspected of having a perceived malaria-related illness received timely appropriate treatment consistent with the Abuja target of treating malaria within 24 h of illness onset; 33% of children received appropriate treatment within 48 h. Reported perceived causes of phlegm predicted timely, appropriate treatment within 24 h of illness onset (P ¼ 0.04) in a multivariate logistic regression model; playing on the ground (P < 0.01) predicted such treatment within 48 h. Two categories of distress, paleness or shortage of blood (P ¼ 0.05) and sweating profusely (P ¼ 0.03), also predicted timely, appropriate treatment within 24 h in a multivariate logistic regression model. Knowing that mosquitoes transmit malaria was not associated with timely, appropriate help seeking for the children, even though such knowledge may promote personal protective measures, especially use of bednets. Patterns of distress and PC were related to timely, appropriate help seeking, but not as expected. Effects on health seeking of illness-related experience and meaning are complex, and explaining their role may strengthen interventions for childhood malaria.