In four dimensions one can use the chiral part of the spin connection as the main object that encodes geometry. The metric is then recovered algebraically from the curvature of this connection. We address the question of how isometries can be identified in this ‘pure connection’ formalism. We show that isometries are recovered from gauge transformation parameters satisfying the requirement that the Lie derivative of the connection along a vector field generating an isometry is a gauge transformation. This requirement can be rewritten as a first order differential equation involving the gauge transformation parameter only. Once a gauge transformation satisfying this equation is found, the isometry generating vector field is recovered algebraically. We work out examples of the new formalism being used to determine isometries, and also prove a general statement: a negative definite connection on a compact manifold does not have symmetries. This is the precise ‘pure connection’ analog of the well-known Riemannian geometry statement that there are no Killing vector fields on compact manifolds with negative Ricci curvature.