Net fluid balance in the Alberta Basin has been negative over the last 60 years because extensive fluid production has consistently exceeded injection during this period. However, future gigaton-scale carbon sequestration, among other activities, can result in future cumulative fluid injection exceeding extraction (i.e., a positive net fluid balance). The in-situ net fluid balance (i.e., total fluids produced minus total fluids injected) in this basin over the period 1960−2020 shows that a liquids deficit of 4.53 × 109 m3 and a gas deficit of 6.05 × 1012 m3 currently exist. However, fluid deficits are more significant in the upper stratigraphic intervals (located more than 1 km above the Precambrian Basement) than in the stratigraphic intervals located within 1 km of the Precambrian Basement in most geographic regions. This observation indicates that greater sustainable injection capacity for large-scale fluid injection may exist in the upper stratigraphic intervals (located at more than 1 km above the Precambrian Basement), reducing the potential for generating induced seismicity of concern. Additionally, while fluid depletion rates consistently increased over most of the last 60 years in the Alberta Basin, this trend appears to have changed over the past few years. Such analysis of regional net fluid balance and trends may be useful in assessing regional sustainable fluid storage capacity and managing induced seismicity hazards.