A critical question regarding TA and 2D-CIVS is whether tag-loss dynamics interfere in the measurement of the desired nonlinear signals of the underlying parent ion. The strong cross peaks observed at 3 ps waiting time in Fig. indicate that tag-loss dynamics are not yet affecting the measurements. If tag loss occurs during the pump-probe waiting time period, the experiment becomes analogous to hole-burning: the pump acts to deplete tagged ion population causing less action signal to be produced by the probe. This would then result in static bleach signals along the diagonal and, importantly, no cross peak signals. It is evident that this is not the case for protonated caffeine. Instead, both intramolecular and intermolecular vibrational relaxation processes appear to occur on relatively long timescales. Solution-phase studies on neutral caffeine measured ~800 fs IVR timescales for the carbonyl stretches with a small solvent dependence. While it is difficult to make quantitative conclusions at the current level of experimental uncertainty, the cross peaks qualitatively appear stronger and more distinct at 3 ps compared to 200 fs, suggesting vibrational energy transfer dynamics between the three modes. Intermolecular relaxation to solvent in neutral caffeine, on the other hand, was measured to occur on ~5 ps (D2O) and ~10 ps (CH3CN) timescales, respectively. Intermolecular relaxation in isolated, cryogenically cooled protonated caffeine to a weakly interacting N2 tag molecule, therefore, likely takes place on timescales >>10 ps. Similarly, the oscillatory intensity modulations measured in our previous TA-CIVS experiments on fac-Re(CO)3(CH3CN)3 + persisted beyond 3 ps waiting time. While not completely general, we posit that intermolecular vibrational relaxation to weakly-bound tags and subsequent tag-loss dynamics will, in most cases, take place on timescales much longer than the dynamics of interest for cryogenically cooled molecular ions.