ObjectiveTo develop and test the model of association of social connectedness and health‐related quality of life (HRQoL) among patients with cancer undergoing chemotherapy and to describe their social connectedness through photo‐elicitation.BackgroundSocial connectedness has been empirically associated with several well‐being outcomes. However, little is known on the association of social connectedness among patients with cancer undergoing chemotherapy.MethodsEmploying a mixed‐methods design following the good reporting of a mixed methods study guideline, the quantitative approach involved 230 consecutively‐selected patients with cancer undergoing chemotherapy who answered a three‐part survey. From these patients, six informants participated in the photo‐elicitation and key informant interview sessions. Gathered data were quantitatively analyzed using structural equation modelling and qualitatively processed using polytextual thematic analysis.Results and FindingsSocial connectedness had a positive influence on social well‐being (β = .22, p = .008) and emotional well‐being (β = .20, p = .023); however, it had a negative effect on functional well‐being (β = −.20, p = .007). The overall model revealed good model indices: χ2/df = .82, RMSEA = .01, GFI = 1.00. Qualitative analysis culled from photo‐elicitation uncovered five interconnected themes yielding the Honeycomb model of social connectedness which was composed of correspondence, cohesion, constitution, convergence and corroboration.ConclusionHRQoL among patients with cancer undergoing chemotherapy is a multi‐factorial health construct affected by social connectedness. The presented model emphasises the importance of social connectedness and paves way for the development of appropriate strategies to promote social connectedness among patients with cancer undergoing chemotherapy.Relevance to Clinical PracticeThe findings provide impetus in the modification and development of appropriate practices, policies and strategies in promoting social connectedness. These approaches are geared towards patient–family empowerment and health education techniques to ascertain that assistance from significant others is provided without limiting the patient's autonomy or independence.