Indoxyl sulfate (IS) and p-cresol sulfate (p-CS) are protein-bound solutes that accumulate in the blood serum in chronic kidney disease and have a detrimental effect on the kidney and other organs' function. This study seeks to define the effectiveness of IS and p-CS clearance after single dialysis sessions and after 8-week-long cycles of hemodialysis using the following different dialysis modalities in succession: low-flux hemodialysis (lfHD), high-flux hemodialysis (hfHD), and post-dilution hemodiafiltration (HDF). We also investigated to what extent IS and p-CS serum content would associate with some other biochemical indices in patients with chronic kidney diseases. The study included 21 uremic patients. We found that a single session of each modality effectively decreased the content of both IS and p-CS, with the predominance of p-CS decrease. There were no appreciable differences depending on the modality of hemodialysis chosen. However, the leaching effect tended to wear off with the weeks' long dialysis cycles. We further found that a greater inflammation-prone level of hsCRP evoked by dialysis led to a greater removal of solutes, and thus their decrease in the serum, during a single dialysis session. Reversely, a greater protein level might result in a greater solute binding and a decrease in removal. We conclude that there are no major differences in the serum clearance of IS and p-CS depending on the dialysis modality. These protein-bound toxins are significantly cleared from the serum already during the first dialysis session, but their level tends to revert during weeks' long dialysis sessions.