Introduction Albumin substantially influences the acid-base equilibrium within the human body and the regulation of acid-base homeostasis. The precise role of albumin remains a subject of debate. Human plasma protein fraction 5% (PPF5%) (Octapharma Pharmazeutika Produktionsgesellschaft m.b.H., Vienna, Austria) contains selected plasma with approximately 88% normal human albumin. We hypothesize that the use of PPF5% in patients undergoing liver resection surgery will enhance tissue perfusion and augment the buffering capacity of blood. Methods A prospective, randomized controlled study spanning 18 months was conducted at Hamad General Hospital, Qatar, involving 48 patients scheduled for liver resection surgeries. Patients were allocated into two groups: group A received an intravenous infusion of PPF5%, while group R received an intravenous infusion of crystalloid (lactated Ringer's solution). Acid-base electrolyte fluctuations were evaluated on four occasions at different time intervals. Results There were significant alterations within each group at different time points. Group A exhibited a substantial variance in strong ion difference (SID) values compared to group R at the time after liver resection (TAR) and at the time of end of surgery (TE). Group A demonstrated significantly enhanced tissue perfusion at TAR and TE relative to group R. There was a noteworthy decrease in hemoglobin and hematocrit levels in group A compared to group R at TE due to the hemodilution effect of the PPF5%. Conclusions The use of PPF5% in significant quantities for rehydration during liver resection procedures appears safe, exhibiting no equivalent alterations in acid-base balance, electrolyte levels, and coagulation when compared to lactated Ringer's solution. Moreover, it demonstrates improved tissue perfusion alongside increased hemodilution.