Blood sample collection is essential for clinical research but can be challenging due to cultural beliefs, emotional responses, and misconceptions. This can escalate in paediatric settings. Despite the growing landscape of clinical research, evidence from South Asia remains limited. This study explores the factors influencing willingness to accept paediatric blood sample collection for clinical research in Nepal, drawing on experiences from a clinical research cohort. A qualitative study grounded in a constructivist-interpretivist paradigm, using semi-structured interviews, was conducted with 38 parents/guardians of sick children attending a study fever clinic. A purposive sampling technique was used to recruit participants attending the study fever clinic at Patan Hospital, Nepal. Additionally, interviews were conducted with six research clinicians and nurses. Interviews were conducted between May 2022 and August 2023. The six-step thematic analysis process described by Braun and Clarke was used to identify key themes and subthemes related to blood collection experiences for research purposes. Willingness to provide consent for paediatric blood sampling was shaped by three inter-related factors: personal, behavioural and environmental. Personal beliefs about blood and blood volume, its replenishment and contribution to public health encouraged participation, while fears of harm and lack of personal benefit deterred consent. Behavioural factors included prior experience of blood collection, professional background and perceived necessity of the test. Environmental influences such as trust in the hospital and research staff, effective communication and family decision-making dynamics, were also critical. Some participants equated research blood collection with altruistic donation, while others expressed concerns about misuse or wastage. Our findings underscore the need to engage with the community regarding beliefs about blood in research, transparent communication and trust-building strategies in paediatric clinical research. These findings offer practical guidance for improving participant recruitment and retention in future clinical research in similar settings.