Spent caustic effluents are very challenging due to their very hazardous nature in terms of toxicity as well as their extreme pH (approximately 12–14). Spent caustic has presented a challenge for wastewater treatment in refineries, due to its composition rich in mercaptans, sulfides and other aromatic compounds. To address such problems, membrane filtration was studied using real effluents from Sines Refinery, in Portugal. The present study attempts to assess the potential for spent caustic treatment with nanofiltration (NF) polymeric and ceramic membranes, assessing membrane life expectancy. For that, membrane aging studies in static mode were performed with the polymeric membrane before attempting NF treatment (dynamic studies). A ceramic membrane was also tested for the first time with this type of effluents, though only in dynamic mode. Although the polymeric membrane performance was very good and in accordance with previous studies, its lifespan was very reduced after 6 weeks of contact with spent caustic, compromising its use in an industrial unit. Contrarily to expectations, the ceramic membrane tested was not chemically more resistant than the polymeric one upon direct contact with spent caustic (loss of retention capacity in less than 1 h in contact with the spent caustic). The results obtained suggest that a pH of 13.9 is very aggressive, even for ceramic membranes.