We present a measurement of the inclusive production of Upsilon mesons in U+U collisions at 193 GeV at mid-rapidity (|y| < 1). Previous studies in central Au+Au collisions at 200 GeV show a suppression of Upsilon(1S+2S+3S) production relative to expectations from the Upsilon yield in p+p collisions scaled by the number of binary nucleon-nucleon collisions (Ncoll), with an indication that the Upsilon(1S) state is also suppressed. The present measurement extends the number of participant nucleons in the collision (Npart) by 20% compared to Au+Au collisions, and allows us to study a system with higher energy density. We observe a suppression in both the Upsilon(1S+2S+3S) and Upsilon(1S) yields in central U+U data, which consolidates and extends the previously observed suppression trend in Au+Au collisions.