Any finite-dimensional p-adic representation of the absolute Galois group of a p-adic local field with imperfect residue field is characterized by its arithmetic and geometric Sen operators defined by Sen-Brinon. We generalize their construction to the fundamental group of a p-adic affine variety with a semi-stable chart, and prove that the module of Sen operators is canonically defined, independently of the choice of the chart. When the representation comes from a Q_p-representation of a p-adic Lie group quotient of the fundamental group, we describe its Lie algebra action in terms of the Sen operators, which is a generalization of a result of Sen-Ohkubo. These Sen operators can be extended continuously to certain infinite-dimensional representations. As an application, we prove that the geometric Sen operators annihilate locally analytic vectors, generalizing a result of Pan.