Cellulose is a very common polymer in domestic wastewater (WW), representing a not negligible part of the organic substance contained in sewage. To date, many studies have highlighted the feasibility of reusing this compound in several ways (e.g., building sector, wastewater treatment, energy production, etc.) after its separation from domestic WW. However, studies about the impact of the absence of cellulose on the chemical and physico-chemical parameters of a biological process are still lacking. In this work, two pilot-scale plants were used to simulate an anoxic treatment of WW in septic tanks, with and without cellulose (CWW and NCWW, respectively), for three months. The results of the monitoring highlighted that T, pH, and electrical conductivity (EC) remained almost constants, in both cases. The Spearman correlation coefficients (SCC) for turbidity (TUR), total suspended solids (TSS), and color (COL) indicated a higher removal in the case of CWW (65%, 66%, and 56%, respectively). Organic substance and nitrogen forms showed a similar behavior with and without cellulose, but in the case of CWW, N-NH3 was highly negatively correlated with TUR (SCC: −0.54), TSS (−0.49), and COL (−0.39). A biological denitrification process was highlighted in both cases. Despite these differences, when statistically analyzing the trends of the chemical and physico-chemical parameters for CWW and NCWW, a significant difference due to the absence of cellulose was excluded. These results will be useful to the scientific community, as they exclude that the operational parameters of anoxic treatments and the effectiveness on pollutants removal can be affected in the case of preliminary cellulose separation from domestic WW for recovery/reuse purposes.