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The involvement of families and communities in healthcare services by healthcare providers enhances accountability towards the community they serve. Guardians need to be involved in the integrated management of childhood illnesses (IMCI) to improve child health outcomes. The study aimed to explore challenges experienced by nurses regarding the involvement of guardians in the management of childhood illnesses in the Vhembe district. A qualitative, exploratory-descriptive design was followed in this study. Fifteen participants were purposefully selected for the study. One-on-one interviews following a semi-structured interview guide were conducted face-to-face with the participants. A voice recorder was used to record the interviews. Data analysis was done following Tesch's eight steps. Trustworthiness was ensured throughout the study. The study yielded two themes, namely: guardians-related challenges, which are lack of knowledge and understanding of IMCI, language barrier and lack of continuity of care and healthcare service-related challenges, which are lack of human resource, staff attitude towards the IMCI strategy, shortage of material resource and erratic water supply. For the strategy to be effective in reducing the complications of childhood illnesses and child mortality, the government needs to avail the required resources and develop measures to empower guardians in child health management.