This paper discusses Ernst Mach's interpretation of the principle of energy conservation (EC) in the context of the development of energy concepts and ideas about causality in nineteenth-century physics and theory of science. In doing this, it focuses on the close relationship between causality, energy conservation and space in Mach's antireductionist view of science. Mach expounds his thesis about EC in his first historical-epistemological essay, "Die Geschichte und die Wurzel des Satzes von der Erhaltung der Arbeit" (1872): far from being a new principle, it is used from the early beginnings of mechanics independently from other principles; in fact, EC is a pre-mechanical principle which is generally applied in investigating nature: it is, indeed, nothing but a form of the principle of causality. The paper focuses on the scientific-historical premises and philosophical underpinnings of Mach's thesis, beginning with the classic debate on the validity and limits of the notion of cause by Hume, Kant, and Helmholtz. Such reference also implies a discussion of the relationship between causality on the one hand and space and time on the other. This connection plays a major role for Mach, and in the final paragraphs its importance is argued in order to understand his antireductionist perspective, i.e. the rejection of any attempt to give an ultimate explanation of the world via reduction of nature to one fundamental set of phenomena.