The kinetics for the isomerization of the 50e cluster Os3(μ-TeTol-p)2(CO)10 (3), where the tellurides bridge two different Os-Os edges, to one in which the tellurides bridge the same open Os···Os edge (4), have been measured experimentally by 1H NMR spectroscopy. The determined activation parameters are ΔH = 77±9 kJ/mol and ΔS = -12±28 J/mol K. The conversion of 3 to 4 has been computationally investigated by electronic structure calculations using the model compound Os3(μ-TeMe)2(CO)10. The computed isomerization pathway is consistent with the kinetic data and the thermodynamic preference for the product stereoisomer that possesses a slipped, eclipsed conformation for the two p-tolyl groups.