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Background: It is desirable that health researchers have the ability to conduct research on health equity and contribute to the development of their national health system and policymaking processes. However, in low- and middle-income countries (LMICs), there is a limited capacity to conduct this type of research due to reasons mostly associated with the status of national (health) research systems. Building sustainable research capacity in LMICs through the triangulation of South–North-South (S-N-S) collaborative networks seems to be an effective way to maximize limited national resources to strengthen these capacities. This article describes how a collaborative project (SDH-Net), funded by the European Commission, has successfully designed a study protocol and a S-N-S collaborative network to effectively support research capacity building in LMICs, specifically in the area of social determinants of health (SDH); this project seeks to elaborate on the vital role of global collaborative networks in strengthening this practice. Methods: The implementation of SDH-Net comprised diverse activities developed in three phases. Phase 1: national level mapping exercises were conducted to assess the needs for SDH capacity building or strengthening in local research systems. Four strategic areas were defined, namely research implementation and system performance, social appropriation of knowledge, institutional and national research infrastructure, and research skills and training/networks. Phase 2: development of tools to address the identified capacity building needs, as well as knowledge management and network strengthening activities. Phase 3: identifying lessons learned in terms of research ethics, and how policies can support the capacity building process in SDH research. Results: The implementation of the protocol has led the network to design innovative tools for strengthening SDH research capacities, under a successful S-N-S collaboration that included national mapping reports, a global open-access learning platform with tools and resources, ethical guidelines for research, policy recommendations, and academic contributions to the global SDH discourse. Conclusions: The effective triangulation of S-N-S partnerships can be of high value in building sustainable research capacity in LMICs. If designed appropriately, these multicultural, multi-institutional, and multidisciplinary collaborations can enable southern and northern academics to contextualize global research according to their national realities