We present a simple mean-field theory to describe the polymer-mediated depletion attraction between colloidal particles that accounts for the polymer’s chain stiffness. We find that for fixed polymer radius of gyration and volume fraction, the strength of this attraction increases with increasing chain stiffness in both dilute and semidilute concentration regimes. In contrast, the range of attraction monotonically decreases with chain stiffness in the dilute regime, while it attains a maximum in the semidilute regime. The obtained analytical expressions for the depletion interaction were compared with numerical self-consistent field lattice computations and shown to be in quantitative agreement. From the interaction potential between two spheres, we calculated the second osmotic virial coefficient B2, which appears to be a convex function of chain stiffness. A minimum of B2 as a function of chain stiffness was observed both in the numerical self-consistent field computations and the analytical theory. These findings help explain the general observation that semiflexible polymers are more effective depletants than flexible polymers and give insight into the phase behavior of mixtures containing spherical colloids and semiflexible polymers.