© 2018 Elsevier B.V. A stack of thin Nb foils was irradiated with the 100 MeV proton beam at Los Alamos National Laboratory's Isotope Production Facility, to investigate the 93Nb(p,4n)90Mo nuclear reaction as a monitor for intermediate energy proton experiments and to benchmark state-of-the-art reaction model codes. A set of 38 measured cross sections for natNb(p,x) and natCu(p,x) reactions between 40–90 MeV, as well as 5 independent measurements of isomer branching ratios, are reported. These are useful in medical and basic science radionuclide productions at intermediate energies. The natCu(p,x)56Co, natCu(p,x)62Zn, and natCu(p,x)65Zn reactions were used to determine proton fluence, and all activities were quantified using HPGe spectrometry. Variance minimization techniques were employed to reduce systematic uncertainties in proton energy and fluence, improving the reliability of these measurements. The measured cross sections are shown to be in excellent agreement with literature values, and have been measured with improved precision compared with previous measurements. This work also reports the first measurement of the natNb(p,x)82mRb reaction, and of the independent cross sections for natCu(p,x)52gMn and natNb(p,x)85gY in the 40–90 MeV region. The effects of natSi(p,x)22,24Na contamination, arising from silicone adhesive in the Kapton tape used to encapsulate the aluminum monitor foils, is also discussed as a cautionary note to future stacked-target cross section measurements. A priori predictions of the reaction modeling codes CoH, EMPIRE, and TALYS are compared with experimentally measured values and used to explore the differences between codes for the natNb(p,x) and natCu(p,x) reactions.