Background: Enhancing the performance of front-line health workers serving vulnerable populations is crucial for redressing inequities. Traditional approaches have focused on introducing technical solutions, such as guidelines and incentives, to modify performance outcomes. Recognition of the complex social nature of health system function draws attention to the intangible software elements that shape performance, including the values, ideas, interests, and norms that guide human behavior and interactions. Insight into the operation of software elements can provide a base for people-focused solutions to support health workers and enable them to confront constraints in low resource settings. This study examines the social environment of the practice of front-line auxiliary nurses (AN) in rural Guatemala, in order to understand the role of health system software elements in enabling their performance and to gain insight into how organizational support can be strengthened through locally-relevant actions. Methods: A mixed methods approach provided a multi-level view of the AN practice environment, situated in the regional health system of the rural department of Alta Verapaz. Interviews with ANs and observations of practice were conducted to understand the values orienting them and how these shaped their relationships with patients and communities. A theory-driven case study of AN supervision was conducted in selected health posts to understand the values orienting supervisors in their role and examine how these shaped their relationships with ANs. The participatory method of concept mapping was used to examine the views of health workers, district and regional managers on actions to strengthen organizational support for the performance of ANs. Results: The values of nursing vocation and community connectedness were prominent in ANs’ interpretations of their work. In relationships, nursing principles oriented them to be attentive to understanding patient needs, and a shared ethnic identity and personal experience of local needs served as a base for engaging with local leaders in community work. The dominant orientation of supervisors in their role was managerial control, and it provided limited support. It contributed to standard-centered relationships with ANs focused on fulfillment of ministry criteria. Supervision oriented by a holistic understanding of ANs’ needs and the goal of improving patient care was more successful in enabling AN motivation. This relationship was characterized as people-centered, based in a shared interpretation of the value of work with patients and the responsive support provided to ANs’ problems. “Organizational climate of support across levels”, where working relationships are characterized by respectful treatment, attention to psycho-social well-being and responsiveness to needs, was identified by health-system actors as a top priority for improving performance. Conclusions: To enable performance, there needs to be a balance between attention to standards and attention to the human dimensions of health worker practice. The dominant approach to supervision did not recognize or build on AN values. Supervision and management should be oriented by a more holistic view of the ANs’ work and their needs, in order to promote a people-centered approach to working relationships. Locally relevant action to strengthen district and regional management’s support for AN performance should focus on operationalizing performance goals that go beyond standards to encompass care that responds to patient and community needs.