A depletion force is an effective attractive force that arises between large colloidal particles that are suspended in a dilute solution of depletants, which are smaller solutes that are preferentially excluded from the vicinity of the large particles. One of the earliest reports of depletion forces that lead to particle coagulation is that of Bondy, who observed the separation or "creaming" of rubber latex upon addition of polymer depletant molecules (sodium alginate) to solution. More generally, depletants can include polymers, micelles, osmolytes, ink, mud, or paint dispersed in a continuous phase.

Depletion forces are often regarded as entropic forces, as was first explained by the established Asakura–Oosawa model. In this theory the depletion force arises from an increase in osmotic pressure of the surrounding solution when colloidal particles get close enough such that the excluded cosolutes (depletants) cannot fit in between them. Because the particles were considered as hard-core (completely rigid) particles, the emerging picture of the underlying mechanism inducing the force was necessarily entropic.

The system of colloids and depletants in solution is typically modeled by treating the large colloids and small depletants as dissimilarly sized hard spheres. Hard spheres are characterized as non-interacting and impenetrable spheres. These two fundamental properties of hard spheres are described mathematically by the hard-sphere potential. The hard-sphere potential imposes steric constraint around large spheres which in turn gives rise to excluded volume, that is, volume that is unavailable for small spheres to occupy.

In a colloidal dispersion, the colloid-colloid interaction potential is approximated as the interaction potential between two hard spheres. For two hard spheres of diameter of ${\displaystyle \sigma }$, the interaction potential as a function of interparticle separation is:

called the hard-sphere potential where ${\displaystyle h}$ is the center-to-center distance between the spheres.

If both colloids and depletants are in a dispersion, there is interaction potential between colloidal particles and depletant particles that is described similarly by the hard-sphere potential. Again, approximating the particles to be hard-spheres, the interaction potential between colloids of diameter ${\displaystyle D}$ and depletant sols of diameter ${\displaystyle d}$ is:

where ${\displaystyle h}$ is the center-to-center distance between the spheres. Typically, depletant particles are very small compared to the colloids so ${\displaystyle d\ll D}$

The underlying consequence of the hard-sphere potential is that dispersed colloids cannot penetrate each other and have no mutual attraction or repulsion.