Honey mesquite [Prosopis glandulosa (Torr.) glandulosa] is a potential foraging resource in southwestern United States rangelands and in other semi-arid rangelands. Yet, intake by ruminants is limited. We conducted an in vitro digestion experiment to assess phenological changes in nutrient value and relative digestibility of honey mesquite leaves, pods, and flowers throughout the 2012 growing season. Crude protein (CP) content of leaves decreased (P < .001) during the year, while acid detergent fiber (ADF) and neutral detergent fiber (NDF) increased (P < .05). Crude protein content of pods decreased (P = .009) over time, but we did not detect (P > .10) any phenological changes in ADF or NDF levels during the study. A cubic response was observed with in vitro gas production and Julian date for both leaves and pods (P ≤ .01). Gas production from leaves collected in spring and early summer were lower than during late summer and early fall. Gas product1ion and nutrient content values suggest that concentration of secondary compounds of mesquite leaves may decrease in late summer. Gas production values of mesquite leaves were lowest in early and mid-summer when CP levels were high and fiber levels were low. Mesquite flowers and pods can be valuable forage resources for cattle. Although mesquite leaves contain nutrients, secondary compounds likely limit intake, especially in late spring and early summer when the CP in mesquite leaves would be most beneficial because quality of herbaceous forages in southwestern United States rangelands at that time is usually low.